Publications by authors named "Nancy Agmon-Levin"

144 Publications

Point of view on the vaccination against COVID-19 in patients with autoimmune inflammatory rheumatic diseases.

RMD Open 2021 02;7(1)

Rheumatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

In view of the COVID-19 pandemic, there is an unmet clinical need for the guidelines on vaccination of patients with autoimmune inflammatory rheumatic diseases (AIIRD). This position paper summarises the current data on COVID-19 infection in patients with AIIRD and development of vaccines against COVID-19, discusses the aspects of efficacy and safety of vaccination, and proposes preliminary considerations on vaccination against COVID-19 in patients with AIIRD, mainly based on the expert opinion and knowledge on the use of other vaccines in this population of patients.
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http://dx.doi.org/10.1136/rmdopen-2021-001594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907831PMC
February 2021

Autoantibodies to Annexin A2 and cerebral thrombosis: Insights from a mouse model.

Lupus 2021 Apr 7;30(5):775-784. Epub 2021 Feb 7.

Department of Neurology, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Ramat Gan, Israel.

Introduction: Antiphospholipid syndrome (APS) is an autoimmune disorder manifested by thromboembolic events, recurrent spontaneous abortions and elevated titers of circulating antiphospholipid antibodies. In addition, the presence of antiphospholipid antibodies seems to confer a fivefold higher risk for stroke or transient ischemic attack. Although the major antigen of APS is β glycoprotein I, it is now well established that antiphospholipid antibodies are heterogeneous and bind to various targets. Recently, antibodies to Annexin A2 (ANXA2) have been reported in APS. This is of special interest since data indicated ANXA2 as a key player in fibrinolysis. Therefore, in the present study we assessed whether anti-ANXA2 antibodies play a pathological role in thrombosis associated disease.

Materials And Methods: Mice were induced to produce anti-ANXA2 antibodies by immunization with ANXA2 (iANXA2) and control mice were immunized with adjuvant only. A middle cerebral artery occlusion stroke model was applied to the mice. The outcome of stroke severity was assessed and compared between the two groups.

Results: Our results indicate that antibodies to ANXA2 lead to a more severe stroke as demonstrated by a significant larger stroke infarct volume (iANXA2 133.9 ± 3.3 mm and control 113.7 ± 7.4 mm; p = 0.017) and a more severe neurological outcome (iANXA2 2.2 ± 0.2, and control 1.5 ± 0.18; p = 0.03).

Conclusions: This study supports the hypothesis that auto-antibodies to ANXA2 are an independent risk factor for cerebral thrombosis. Consequently, we propose screening for anti-ANXA2 antibodies should be more widely used and patients that exhibit the manifestations of APS should be closely monitored by physicians.
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http://dx.doi.org/10.1177/0961203321992117DOI Listing
April 2021

Quality of life of patients with thyroid eye disease: 3-year follow-up in a multidisciplinary clinic in Israel.

Graefes Arch Clin Exp Ophthalmol 2021 Feb 2. Epub 2021 Feb 2.

Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer, Israel.

Background: Changes in the quality of life (QOL) of patients with thyroid eye disease (TED) were examined during a 3-year follow-up in a multidisciplinary eye clinic, and factors that may improve QOL were identified.

Methods: A retrospective review of medical records of all patients who attended the TED clinic at Sheba Medical Center, Israel, from May 2016 to May 2019 was performed. The retrieved data included demographics, comprehensive ophthalmic examination findings, clinical activity scores (CAS), laboratory test results, and QOL assessments by the Graves' Orbitopathy QOL (GO-QOL) questionnaire.

Results: One hundred thirty-two TED clinic patients were examined. Thirty patients (22.72%) received medical treatment consisting of steroids according to the European Group on Graves' Orbitopathy (EUGOGO) protocol, high-dose steroids, or immunosuppressive drugs. Twenty-eight patients (21.21%) underwent surgical rehabilitation (decompression, strabismus, or eyelid surgery). There was a significant increase in total QOL score after steroid treatment according to the EUGOGO protocol, after decompression surgery, and after strabismus surgery compared to pre-treatment total QOL (p=0.04, p=0.021, and p=0.042, respectively, matched pairs). In addition, there were significant positive correlations between the changes in the total QOL score and the change in thyroid-stimulating immunoglobulin (TSI) as well as the change in CAS among the patients who underwent medical and surgical interventions.

Conclusions: QOL improved significantly after medical/surgical treatments. A change in the CAS and in the TSI may also correlate with change in QOL. Periodic evaluation of TED patients' QOL is recommended for enhanced and more comprehensive management.
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http://dx.doi.org/10.1007/s00417-021-05103-5DOI Listing
February 2021

Minor Clinical Impact of COVID-19 Pandemic on Patients With Primary Immunodeficiency in Israel.

Front Immunol 2020;11:614086. Epub 2021 Jan 14.

The Jeffrey Modell Foundation Israeli Network for Primary Immunodeficiency, New York, NY, United States.

In the last few months the world has witnessed a global pandemic due to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection causing coronavirus disease 2019 (COVID-19). Obviously, this pandemic affected individuals differently, with a significant impact on populations considered to be at high-risk. One such population, was assumed to be patients with primary genetic defect involving components or pathways of the immune system. While human immunity against COVID-19 is not fully understood, it is, so far, well documented, that both adaptive and innate cells have a critical role in protection against SARS-CoV-2. Here, we aimed to summarize the clinical and laboratory data on primary immunodeficiency (PID) patients in Israel, who were tested positive for SARS-CoV-2, in order to estimate the impact of COVID-19 on such patients. Data was collected from mid-February to end-September. During this time Israel experienced two "waves" of COVID-19 diseases; the first, from mid-February to mid-May and the second from mid-June and still ongoing at the end of data collection. A total of 20 PID patients, aged 4 months to 60 years, were tested positive for SARS-CoV-2, all but one, were detected during the second wave. Fourteen of the patients were on routine monthly IVIG replacement therapy at the time of virus detection. None of the patients displayed severe illness and none required hospitalization; moreover, 7/20 patients were completely asymptomatic. Possible explanations for the minimal clinical impact of COVID-19 pandemic observed in our PID patients include high level of awareness, extra-precautions, and even self-isolation. It is also possible that only specific immune pathways (e.g. type I interferon signaling), may increase the risk for a more severe course of disease and these are not affected in many of the PID patients. In some cases, lack of an immune response actually may be a protective measure against the development of COVID-19 sequelae.
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http://dx.doi.org/10.3389/fimmu.2020.614086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840610PMC
February 2021

Gender differences in clinical presentation and prognosis of thyroid eye disease.

Eur J Ophthalmol 2020 Nov 6:1120672120964112. Epub 2020 Nov 6.

Goldschleger Eye Institute, Sheba Medical Center, Tel-Hashomer, Israel.

Objective: To examine the clinical differences in manifestation, treatment, and prognosis of thyroid-eye-disease (TED) between men and women.

Methods: This is a longitudinal cohort study. Men and women, who diagnosed with TED and treated at a multidisciplinary TED clinic, were compared regarding differences in demographics, eye examination, disease activity, and quality of life evaluation.

Results: TED was diagnosed in 132 patients during the study period, and they included 38 men (28.78%) and 94 women (71.21%). There were six men and 20 women with active disease (Clinical-Activity-Score (CAS) ⩾ 3) during the entire follow-up period ( < 0.01). The mean time from TED diagnosis to CAS ⩾ 3 was 4.50 years for men and 2.35 years for women ( = 0.05). There were no significant differences in mean total Graves' Orbitopathy-Quality-of-Life questionnaire (GO-QOL) score. However, mean GO-QOL subtotal score of external appearance of women was significantly lower compare to men in the first and last visit ( = 0.04, 0.03, respectively).

Conclusion: Active disease was more common in women and the time-from-diagnosis of TED to CAS ⩾ 3 was shorter among women. Moreover, the appearance QOL score of women was poorer. These findings should be taken into consideration when planning the timing of treatment and when choosing the best treatment for TED patients.
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http://dx.doi.org/10.1177/1120672120964112DOI Listing
November 2020

Antiphospholipid antibodies may be associated with uveitis.

Eur J Ophthalmol 2020 Nov 4:1120672120968729. Epub 2020 Nov 4.

Clinical Immunology, Angioedema and Allergy Unit, Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Israel.

Purpose: To evaluate the prevalence of a spectrum of autoantibodies in adult patients with non-infectious uveitis compared to healthy controls.

Methods: This is a case-control study conducted in a tertiary referral center. Serum positivity to auto-antibodies directed at membranous phospholipids (aPL), nuclear antigens, and cytoplasmic (ANCA) antigens were assessed in sera from 63 non-infectious uveitis patients, and 78 healthy controls. Uveitis patients' demographic and clinical data were collected retrospectively from their medical charts.

Results: Of the spectrum of antibodies evaluated only aPL were linked with uveitis (OR 11.2, CI 1.4-92.1), as 13 (20.6%) uveitis patients were positive to at least one of the screened aPL, namely either anti-cardiolipin (aCL), anti-β2-glycoprotein (aβ2GPI), or anti-phosphatidylserine/prothrombin (aPS/PT). aCL antibodies were detected in 5/63 (7.9%) of uveitis patients and in none of controls ( = 0.016). Positivity to either aCL or aβ2GPI was noted in 8/63 (12.7%) of uveitis patients and in 1 (1.3%) of the controls ( = 0.011). Of the 13 uveitis patients positive to any of the aPL antibodies, 8 (62%) had exclusively anterior uveitis, 9 (69%) were idiopathic, and none had evidence of posterior vaso-occlusive involvement or systemic thrombotic manifestations.

Conclusion: An association between aPL and uveitis among an unselected population of patients with no evidence of thrombosis or presence of the antiphospholipid syndrome was documented in this study. This link was observed, alike the general population of uveitis patients, mainly in patients with anterior eye inflammation. A possible interaction between aPL and uveitis, mediated by non-thrombotic mechanisms, requires further studies.
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http://dx.doi.org/10.1177/1120672120968729DOI Listing
November 2020

Rituximab for refractory manifestations of the antiphospholipid syndrome: a multicentre Israeli experience.

Clin Exp Rheumatol 2020 Oct 27. Epub 2020 Oct 27.

Sackler School of Medicine, Tel-Aviv University, and Department of Rheumatology, Tel Aviv Medical Center, Israel.

Objectives: The clinical manifestations of the antiphospholipid syndrome (APS) are heterogeneous and related to anti-phospholipid antibodies (aPL). There is some evidence that B cells are involved in the pathogenesis of this condition. Thus the ability of rituximab (RTX) to deplete B cells makes it an appealing potential therapy for refractory antiphospholipid syndrome (APS). Real world data on RTX treatment of APS are still lacking. This study was conducted to report outcomes of RTX administration in the treatment of different aspects of APS.

Methods: This is a retrospective case series study on APS patients from 3 medical centres in Israel who were treated with RTX during 2010-2019 for refractory manifestations of APS including diffuse alveolar haemorrhage, recurrent thrombosis, cytopenia, neurological and skin manifestations. Medical records were reviewed regarding the clinical indication for RTX treatment, concomitant medications, RTX protocol, aPL status and response to treatment. Outcomes were defined as complete response if full resolution of the "indicated manifestation" was achieved and maintained for at least 12 months, partial response or no response.

Results: We identified 40 APS patients who were treated with RTX for refractory manifestations of this condition, of whom, 24 patients (60%) were female with a mean age of 40 years, and 31 patients (78%) were diagnosed with primary APS. A favourable response to RTX was documented in 32 patients (80%) including a complete response in 22 patients (55%). Response to RTX treatment was associated with a rituximab protocol of 375mg/m2 x 4 compared to a fixed dose of 1000 mg x2 (100% vs. 65%; p=0.01). Complete response was associated with a decrease in aPL titres within 4-6 months post treatment, whereas no significant change in aPL titres was observed in patients with partial or no response.

Conclusions: Consistent with previous small case series, we report a good therapeutic response to RTX in patients with difficult to treat manifestations of APS. In this cohort, treatment protocols were associated with outcomes. Although further studies are required to verify our observations, our data support a plausible role for B cell depletion in refractory APS.
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October 2020

Efficacy of omalizumab treatment for pediatric chronic spontaneous urticaria: A multi-center retrospective case series.

Pediatr Dermatol 2020 Nov 19;37(6):1051-1054. Epub 2020 Sep 19.

Kipper Institute of Immunology and Allergy, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

Background: Chronic urticaria is defined by the presence of itchy wheals, sometimes accompanied by angioedema, lasting for at least 6 weeks. In children, most cases occur without an eliciting factor and are defined as chronic spontaneous urticaria (CSU). CSU affects up to 0.75% of children with a negative impact on quality of life and school performance. CSU is treated in adults with second-generation antihistamines, increased up to four times normal doses for second-line treatment. Omalizumab (a monoclonal antibody to IgE) may be recommended as third-line therapy. A similar protocol is used in children, yet little is known of its efficacy and safety.

Objectives: To summarize our multi-center experience in treating children with recalcitrant CSU with omalizumab.

Methods: A retrospective multi-center case series conducted in 5 tertiary care centers in Israel. Patients included were children <18 years old diagnosed with recalcitrant CSU who were treated with omalizumab. Patients were followed up throughout the duration of omalizumab therapy/symptom remission. Patients' electronic medical records were used to gather data.

Results: Nineteen participants (11 F; 8 M) presented with CSU between ages 6 and 16.9 years. Sixteen (84%) responded to omalizumab, including children <12 years old, although two became non-responsive after 6-12 months of therapy. Another three patients (16%) were resistant to treatment, achieving remission through fourth-line (Cyclosporine A) or other therapies.

Conclusion: Children with recalcitrant CSU, even those <12 years old, respond well to standard-dose, third-line omalizumab therapy at rates similar to adults. Yet, some cases may become non-responsive with ongoing treatment.
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http://dx.doi.org/10.1111/pde.14360DOI Listing
November 2020

Combination therapy with omalizumab and an immune-suppressive agent for resistant chronic spontaneous rrticaria - A real-life experience.

World Allergy Organ J 2020 Aug 4;13(8):100448. Epub 2020 Aug 4.

Clinical Immunology, Angioedema and Allergy Unit, Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Israel.

Background: Chronic Spontaneous Urticaria (CSU) is a relatively common immune mediated disease that can be effectively treated nowadays. Nevertheless, for some patients remission cannot be achieved following current treatment recommendations, defined as resistant CSU (r-CSU). Treating r-CSU is challenging, and, currently, there are no recommended interventions. In this real-life study we describe successful therapy of 18 r-CSU patients using an "intensified protocol" of anti-IgE-antibody (omalizumab) concomitantly with an immunosuppressant. We defined the r-CSU phenotype and compared it to omalizumab-responsive CSU (Or-CSU) phenotype.

Methods: Clinical and serological data of 72 CSU patients (ie, 18 r-CSU and 54 age and sex matched Or-CSU) were retrospectively collected and analyzed. All patients were diagnosed with CSU for ≥6 months and treated at the Sheba Medical Center during 2013-2018.

Results: Of 289 CSU patients, 18 (6%) were diagnosed with r-CSU and treated with the "intensified protocol" including omalizumab and cyclosporine-A (16p), methotrexate (1p), and azathioprine (1p). Of which, 14/18 (78%) achieved complete remission, 2/18 (11%) partial remission, and 2/18 (11%) no remission. During follow-up no serious adverse events were documented. r-CSU patients received higher doses of antihistamine (p < 0.0001) and omalizumab (425 ± 58 mg/month vs. 283 ± 86 mg/month; p < 0.0001) compared to Or-CSU. The r-CSU phenotype was linked with concomitant autoimmunity (p = 0.0005) and a lower level of IgE prior to initiation of therapy (p = 0.027).

Conclusion: r-CSU may be a distinct CSU phenotype characterized by severe disease, concomitant autoimmunity, and lower baseline-IgE levels (low "autoallergy"). An "intensified protocol" with omalizumab and an immunosuppressive agent was found to be efficacious and safe for r-CSU. Further larger studies are required to verify these results.
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http://dx.doi.org/10.1016/j.waojou.2020.100448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403771PMC
August 2020

Profiles of criteria and non-criteria anti-phospholipid autoantibodies are associated with clinical phenotypes of the antiphospholipid syndrome.

Auto Immun Highlights 2020 Dec 15;11(1). Epub 2020 May 15.

1Clinical Immunology, Angioedema and Allergy Unit, Zabludowicz Center for Autoimmune Diseases, The Chaim Sheba Medical Center, Tel-Hashomer, 52621 Israel.

Background: Specific anti-phospholipids antibodies (aPLs) are used as classification criteria of the antiphospholipid syndrome (APS). These aPLs, although essential for diagnosis, do not predict disease phenotypes, which may require specific therapies. Non-criteria aPLs are rarely evaluated and their role is yet to be defined. In the current study, we aimed to examine the association between criteria and non-criteria aPLs and APS phenotypes.

Methods: Serum samples from 188 subjects, 130 APS patients and 58 controls were analyzed for the presence of 20 aPLs (IgG and IgM isotypes to cardiolipin (CL), beta2-glycoprotein1 (β2GP1), phosphatidic acid (P-acid), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylinositol (PI), phosphatidylserine (PS), annexin-5 (AN) and prothrombin (PT) using a line immunoassay (GA Generic Assays, Germany). Sero-positivity to the different aPLs/aPLs profiles was correlated to APS phenotypes (i.e. arterial thrombosis, CNS manifestations, venous thrombosis, relapsing disease, obstetric morbidity).

Results: In this cohort, arterial thrombosis was associated with accumulative number of ≥ 7/20 aPLs evaluated (OR 4.1; CI 95% 1.9-96, p = 0.001) as well as the sole presence of aPT (IgG) (OR 2.3;CI 95% 1.1-5.1, p = 0.03). CNS manifestations were linked with a profile of 4 aPLs (IgG): aPT, aPG, aPI and aAN (OR 2.6;CI 95% 1.1-6.3, p = 0.03). Symptom-free period of ≥ 3 years was linked with lower number of aPLs and the presence of aPI (IgG) (OR 3.0;CI 95% 1.08-8.1, p < 0.05) or aAN (IgG) (OR 3.4;CI 95% 1.08-10.9, p < 0.05). APS related pregnancy morbidity correlated with a profile of 2 aPLs (IgG): aCL and aPS (OR 2.9; CI 95% 1.3-6.5, p < 0.05) or the sole presence of aAN (IgG) (OR 2.8; CI 95% 1.02-8, p = 0.05).

Conclusion: In this study, we observed an association between specific criteria/non-criteria aPLs or aPLs profiles and clinical phenotypes of APS. Our data suggest that examination of a wider variety of aPLs may allow better characterization of APS.
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http://dx.doi.org/10.1186/s13317-020-00131-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229627PMC
December 2020

Clinical characteristics and management of chronic spontaneous urticaria in patients refractory to H-Antihistamines in Asia, Middle-East and Africa: Results from the AWARE-AMAC study.

World Allergy Organ J 2020 Apr 30;13(4):100117. Epub 2020 Apr 30.

Novartis Pharma AG, Basel, Switzerland.

Background: Chronic urticaria (CU) is a condition characterized by recurrent itchy hives and/or angioedema for ≥6 weeks. Most of the data about CU come from western countries with very little information available about CU in Asia, Africa, and the Middle East.

Methods: AWARE-AMAC is a 24-month prospective, observational, real-world, non-interventional study in patients aged ≥18 years from Asia, the Middle East, and Africa (AMAC) with CU refractory to H1-antihistamines (H1-AH). The main objective was to describe the real-world experience with CU, including clinical characteristics, presence of angioedema, treatment patterns (shifts between treatment classes and changes within a treatment class), investigator-assessed disease control, and the impact on quality of life. Subgroups of interest were type of CU at Baseline and treatment class (based on 2013 urticaria guidelines). There were no mandatory visits and diagnostic/monitoring procedures additional to routine practice, except the patient diary (7-day Urticaria Activity Score) and patient reported outcome assessments.

Results: The focus of the current manuscript is on patients with chronic spontaneous urticaria (CSU), who formed 98% of the sample. Patients were predominantly female (69.6% female, mean age ± SD 39.8 ± 13.29 years). Time since current diagnosis (Mean ± SD) was 28.6 ± 49.06 months. Amongst patients with CSU, 31.0% had comorbid chronic inducible urticaria (CINDU) and 46.4% had a history of angioedema. 91.9% received H1-AH therapy (±other treatments). The most frequently prescribed treatment classes at Baseline were any/combination of medications, not classified under the other 7 treatment classes, named "Others" (30.5%) followed by, omalizumab (OMA; 23.6%) and second-generation H1-AH monotherapy (sgAH; 15.1%). At Month 12, the most prescribed treatment classes (>15%) for patients were OMA (23.5%) and "Other" (21.3%); 19.7% received "No drug". At Month 24, OMA (22.5%), and "Other" (17.9%) were most frequently prescribed; 28.6% received "No drug". Overall, 79.5% of patients had some type of change in treatment. Over the study period, improvement in self-reported QoL increased, which was mirrored by better disease control.

Conclusion: In AMAC countries, the non-recommended "Other" treatment class played a major role in the initial management of CU patients. High usage of H1-AH (±other treatments) and OMA was observed. Treatment changes were observed in a majority of patients. Treatment escalation from sgAH was mostly via OMA. Improvement of disease control and QoL was achieved during the study period.

Trial Registration: Observational study (NA).
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http://dx.doi.org/10.1016/j.waojou.2020.100117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200453PMC
April 2020

Small-fiber neuropathy associated with autoinflammatory syndromes in children and adolescents.

Muscle Nerve 2020 06 17;61(6):791-796. Epub 2020 Mar 17.

Institute of Pediatric Neurology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

Introduction: Small-fiber neuropathy is rare in children. It has been associated with several autoimmune disorders, but there are no reports of an autoinflammatory etiology.

Methods: The data of four children/adolescents presenting with erythromelalgia and neuropathic pain from 2014 to 2019 were collected retrospectively from the electronic database of a pediatric medical center.

Results: Results of clinical and/or electrophysiological evaluation excluded large nerve fiber involvement. Skin biopsy results confirmed small-fiber neuropathy. According to genetic analysis, two patients were heterozygous and one was homozygous for mutations in the familial Mediterranean fever (MEFV) gene. Behcet disease was diagnosed in the fourth patient. Treatment with anti-interleukin-1 agents, intravenous immunoglobulin, and glucocorticoids was beneficial.

Discussion: The diagnosis of small-fiber neuropathy should be considered in children/adolescents presenting with erythromelalgia. A thorough investigation is required to reveal the underlying disorder. Clinicians should be alert to the peripheral neurological manifestations of autoinflammatory syndromes because effective treatments are available.
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http://dx.doi.org/10.1002/mus.26857DOI Listing
June 2020

The innate immune perspective of autoimmune and autoinflammatory conditions.

Rheumatology (Oxford) 2019 11;58(Suppl 6):vi1-vi8

Clinical Immunology, Angioedema and Allergy Unit, The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Tel Aviv, Israel.

Innate immunity is one of two immune defence system arms. It is present at birth and does not require 'learning' through exposure to foreign organisms. It activates various mechanisms collectively to eliminate pathogens and hold an infection until the adaptive response are mounted. The innate immune system consists of four elements: the epithelial barrier, cells (e.g. macrophages, NK cells), plasma proteins (e.g. complement) and cytokines. These components act in concert to induce complex processes, as well as recruitment, activation and differentiation of adaptive responses. The innate response is more than just the 'first line of defence', as it essentially withholds the vast majority of any intruder, has a complex interplay with the adaptive arm and is crucial for survival of the host. Finally, yet importantly, a myriad of diseases has been linked with innate immune dysregulation. In this mini-review we will shed some light on these conditions, particularly regarding autoinflammatory ones.
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http://dx.doi.org/10.1093/rheumatology/kez387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878844PMC
November 2019

Incidence and prevalence of vaccine preventable infections in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD): a systemic literature review informing the 2019 update of the EULAR recommendations for vaccination in adult patients with AIIRD.

RMD Open 2019 19;5(2):e001041. Epub 2019 Sep 19.

Department of Rheumatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

Objectives: The aims of this study were to update the evidence on the incidence and prevalence rates of vaccine preventable infections (VPI) in patients with autoimmune inflammatory rheumatic diseases (AIIRD) and compare the data to the general population when available.

Methods: A literature search was performed using Medline, Embase and Cochrane library (October 2009 to August 2018). The primary outcome was the incidence or prevalence of VPI in the adult AIIRD population. Meta-analysis was performed when appropriate.

Results: Sixty-three publications out of 3876 identified records met the inclusion criteria: influenza (n=4), pneumococcal disease (n=7), hepatitis B (n=10), herpes zoster (HZ) (n=29), human papillomavirus (HPV) infection (n=13). An increased incidence of influenza and pneumococcal disease was reported in patients with AIIRD. HZ infection-pooled incidence rate ratio (IRR) was 2.9 (95% CI 2.4 to 3.3) in patients with AIIRD versus general population. Among AIIRD, inflammatory myositis conferred the highest incidence rate (IR) of HZ (pooled IRR 5.1, 95% CI 4.3 to 5.9), followed by systemic lupus erythematosus (SLE) (pooled IRR 4.0, 95% CI 2.3 to 5.7) and rheumatoid arthritis (pooled IRR 2.3, 95% CI 2.1 to 2.6). HPV infection-pooled prevalence ratio was 1.6, 95% CI 0.7 to 3.4 versus general population, based on studies mainly conducted in the SLE population in Latin America and Asia. Pooled prevalence of hepatitis B surface antigen and hepatitis B core antibody in patients with AIIRD was similar to the general population, 3%, 95% CI 1% to 5% and 15%, 95% CI 7% to 26%, respectively.

Conclusion: Current evidence shows an increased risk of VPI in patients with AIIRD, emphasising that prevention of infections is essential in these patients.
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http://dx.doi.org/10.1136/rmdopen-2019-001041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6803008PMC
April 2020

Efficacy, immunogenicity and safety of vaccination in adult patients with autoimmune inflammatory rheumatic diseases: a systematic literature review for the 2019 update of EULAR recommendations.

RMD Open 2019 9;5(2):e001035. Epub 2019 Sep 9.

Rheumatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

Aim: To present a systematic literature review (SLR) on efficacy, immunogenicity and safety of vaccination in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD), aiming to provide a basis for updating the EULAR evidence-based recommendations.

Methods: An SLR was performed according to the standard operating procedures for EULAR-endorsed recommendations. Outcome was determined by efficacy, immunogenicity and safety of vaccination in adult patients with AIIRD, including those receiving immunomodulating therapy. Furthermore, a search was performed on the effect of vaccinating household members of patients with AIIRD on the occurrence of vaccine-preventable infections in patients and their household members (including newborns). The literature search was performed using Medline, Embase and the Cochrane Library (October 2009 to August 2018).

Results: While most investigated vaccines were efficacious and/or immunogenic in patients with AIIRD, some were less efficacious than in healthy control subjects, and/or in patients receiving immunosuppressive agents. Adverse events of vaccination were generally mild and the rates were comparable to those in healthy persons. Vaccination did not seem to lead to an increase in activity of the underlying AIIRD, but insufficient power of most studies precluded arriving at definite conclusions. The number of studies investigating clinical efficacy of vaccination is still limited. No studies on the effect of vaccinating household members of patients with AIIRD were retrieved.

Conclusion: Evidence on efficacy, immunogenicity and safety of vaccination in patients with AIIRD was systematically reviewed to provide a basis for updated recommendations.
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http://dx.doi.org/10.1136/rmdopen-2019-001035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744079PMC
April 2020

Pulmonary Endarterectomy Surgery for Chronic Thromboembolic Pulmonary Hypertension: A Small-Volume National Referral Center Experience.

Isr Med Assoc J 2019 Aug;21(8):528-531

Department of Cardiac Surgery, Leviev Heart Center, Sheba Medical Center, Tel Hashomer, Israel.

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, distinct pulmonary vascular disease, which is caused by chronic obstruction of major pulmonary arteries. CTEPH can be cured by pulmonary endarterectomy (PEA). PEA for CTEPH is a challenging procedure, and patient selection and the perioperative management are complex, requiring significant experience.

Objectives: To describe the establishment of a national CTEPH-PEA center in Israel and present results of surgery.

Methods: In this study, we reviewed the outcomes of PEA in a national referral, multi-disciplinary center for CTEPH-PEA. The center was established by collaborating with a high-volume center in Europe. A multidisciplinary team from our hospital (pulmonary hypertension specialist, cardiac surgeon, cardiac anesthesiologist and cardiac surgery intensivist was trained under the guidance of an experienced team from the European center.

Results: A total of 38 PEA procedures were performed between 2008 and 2018. We included 28 cases in this analysis for which long-term follow-up data were available. There were two hospital deaths (7%). At follow-up, median New York Heart Association (NYHA) class improved from III to I (P < 0.0001), median systolic pulmonary pressure decreased from 64 mmHg to 26 mmHg (P < 0.0001), and significant improvements were seen in right ventricular function and exercise capacity.

Conclusions: A national center for performance of a rare and complex surgical procedure can be successfully established by collaboration with a high-volume center and by training a dedicated multidisciplinary team.
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August 2019

A structured graduated protocol with heat denatured eggs in the treatment of egg allergy.

Pediatr Allergy Immunol 2019 12 15;30(8):824-832. Epub 2019 Nov 15.

Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

Background: Most children with egg allergy (EA) can tolerate extensively heated and baked egg (EHBE). Consumption of EHBE may promote faster resolution of EA; however, no consensus exists as to the required amounts and treatment protocols.

Objective: To evaluate the efficacy and safety of a structured graduated exposure protocol (SGEP) with EHBE in promoting tolerance to eggs in EA children under 2 years of age.

Methods: In a case-control study, EA children aged < 2 years who were treated with SGEP including EHBE were compared to children treated with strict avoidance. Data were collected from records and telephone questionnaires. Analysis was performed using non-parametric Kaplan-Meier and Cox proportional hazard regression models.

Results: Thirty-nine egg-allergic children with a median age at intervention of 16 months (interquartile range: 13-19) were treated with SGEP and followed to a median age of 39 months (26.8-50.0). The median age at resolution of EA was compared to a matched group of 80 children treated with strict avoidance at least until 2 years of age or earlier natural resolution and followed to a median age of 69 months (46-104). The median estimated age at EA resolution in the SGEP group was 24 months (95% CI, 19.5-28.5 months), compared to 78 months (95% CI, 53-102) in the control group, P < .001. At last follow-up, 82% of treated children were tolerant to lightly cooked eggs vs 54% of controls, P = .001.

Conclusion: A structured protocol with EHBE appears to promote faster resolution of EA.
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http://dx.doi.org/10.1111/pai.13115DOI Listing
December 2019

2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases.

Ann Rheum Dis 2020 01 14;79(1):39-52. Epub 2019 Aug 14.

Rheumatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

To update the European League Against Rheumatism (EULAR) recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) published in 2011. Four systematic literature reviews were performed regarding the incidence/prevalence of vaccine-preventable infections among patients with AIIRD; efficacy, immunogenicity and safety of vaccines; effect of anti-rheumatic drugs on the response to vaccines; effect of vaccination of household of AIIRDs patients. Subsequently, recommendations were formulated based on the evidence and expert opinion. The updated recommendations comprise six overarching principles and nine recommendations. The former address the need for an annual vaccination status assessment, shared decision-making and timing of vaccination, favouring vaccination during quiescent disease, preferably prior to the initiation of immunosuppression. Non-live vaccines can be safely provided to AIIRD patients regardless of underlying therapy, whereas live-attenuated vaccines may be considered with caution. Influenza and pneumococcal vaccination should be strongly considered for the majority of patients with AIIRD. Tetanus toxoid and human papilloma virus vaccination should be provided to AIIRD patients as recommended for the general population. Hepatitis A, hepatitis B and herpes zoster vaccination should be administered to AIIRD patients at risk. Immunocompetent household members of patients with AIIRD should receive vaccines according to national guidelines, except for the oral poliomyelitis vaccine. Live-attenuated vaccines should be avoided during the first 6 months of life in newborns of mothers treated with biologics during the second half of pregnancy. These 2019 EULAR recommendations provide an up-to-date guidance on the management of vaccinations in patients with AIIRD.
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http://dx.doi.org/10.1136/annrheumdis-2019-215882DOI Listing
January 2020

A Structured Gradual Exposure Protocol to Baked and Heated Milk in the Treatment of Milk Allergy.

J Pediatr 2018 12 27;203:204-209.e2. Epub 2018 Sep 27.

Clinical Allergy and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Clalit Health Services, Tel Aviv, Israel; Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel; Allergy and Clinical Immunology Unit, Sheba Medical Center, Tel Hashomer, Israel.

Objective: To evaluate the efficacy and safety of a structured gradual exposure protocol (SGEP) with extensively heated and baked milk in promoting allergy resolution in children with cow milk allergy (CMA).

Study Design: In a case control study, children with CMA aged 1-4 years who were treated with SGEP including extensively heated and baked milk, were compared with children treated with strict avoidance. Data were collected from medical records and from validated telephone questionnaires. Data analysis was performed using a nonparametric Kaplan-Meier and proportional hazard Cox regression model, after evaluation of the adequacy of the case control matching.

Results: There were 43 children with milk allergy-26 (62%) males with a mean age at intervention of 21 months (range, 12-47 months)-who were treated with SGEP and followed to a mean age of 40 months (range, 20-82 months). The median age at resolution of CMA was compared with a matched group of 67 children treated with strict avoidance at least until 4 years of age or followed until earlier resolution, with a mean age at follow-up of 71 months (range, 11-176 months). The median estimated age at CMA resolution in the SGEP group was 36 months (95% CI, 34.5-49.7) compared with 98 months (95% CI, 82.4-114.1) in controls (P < .001). At last follow-up, 86% of treated children were tolerant to unheated milk proteins vs 52% of controls (P = .003).

Conclusion: A structured protocol with extensively heated and baked milk seems to promote faster resolution of CMA.
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http://dx.doi.org/10.1016/j.jpeds.2018.07.091DOI Listing
December 2018

A Prospective International Study on Adherence to Treatment in 305 Patients With Flaring SLE: Assessment by Drug Levels and Self-Administered Questionnaires.

Clin Pharmacol Ther 2019 08 2;106(2):374-382. Epub 2018 Sep 2.

Centre for Rheumatology, University College London, London, UK.

Nonadherence to treatment is a major cause of lupus flares. Hydroxychloroquine (HCQ), a major medication in systemic lupus erythematosus, has a long half-life and can be quantified by high-performance liquid chromatography. This international study evaluated nonadherence in 305 lupus patients with flares using drug levels (HCQ < 200 ng/ml or undetectable desethylchloroquine), and self-administered questionnaires (MASRI < 80%). Drug levels defined 18.4% of the patients as severely nonadherent. In multivariate analyses, younger age, nonuse of steroids, higher body mass index, and unemployment were associated with nonadherence by drug level. Questionnaires classified 23.4% of patients as nonadherent. Correlations between adherence measured by questionnaires, drug level, and physician assessment were moderate. Both methods probably measured two different patterns of nonadherence: self-administered questionnaires mostly captured relatively infrequently missed tablets, while drug levels identified severe nonadherence (i.e., interruption or erratic tablet intake). The frequency with which physicians miss nonadherence, together with underreporting by patients, suggests that therapeutic drug monitoring is useful in this setting. (Trial registration: ClinicalTrials.gov: NCT01509989.).
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http://dx.doi.org/10.1002/cpt.1194DOI Listing
August 2019

Genetic Factors of Autoimmune Diseases 2017.

J Immunol Res 2017;2017:2789242. Epub 2017 Nov 5.

Lupus Clinic, Reumatologia, Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Rome, Italy.

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http://dx.doi.org/10.1155/2017/2789242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5706077PMC
January 2019

Clinical Problem Solving: A Tobacco Merchant Who Can't Spit.

Isr Med Assoc J 2017 Dec;19(12):786-791

Dysautonomia Clinic, Hypertension Unit, Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Israel.

Background: A 47 year old man presented with a combination of dry mouth and lightheadedness while standing. His medical background was unremarkable except for cigarette smoking and hyperlipidemia. Sjögren's syndrome was ruled out, and he was referred for evaluation of orthostatic hypotension, which by then included syncopal episodes and injuries. Additional symptoms included dry eyes, constipation, reduced sweating, and erectile dysfunction. After excluding medications and structural cardiac abnormalities as causes of orthostatic hypotension, a clinical autonomic evaluation was performed. The pattern of beat-to-beat blood pressure associated with performance of the Valsalva maneuver, and a low plasma norepinephrine level that did not increase in response to standing, established that the orthostatic hypotension was neurogenic. Treatment with an alpha-adrenoceptor agonist and fludrocortisone yielded partial improvement. After systemic diseases involving autonomic failure were excluded, cardiac sympathetic neuroimaging was performed by 123I-metaliodobenzylguanidine (MIBG) scanning. The normal uptake seen in the heart indicated intact post ganglionic sympathetic innervation. There were no signs of central neurodegeneration or peripheral neuropathy. Because of symptoms and signs of both parasympathetic and sympathetic failure without denervation, an autonomic ganglionopathy was considered. A high titer of antibody to the neuronal nicotinic receptor, which mediates ganglionic neurotransmission, was obtained. The diagnosis of autoimmune autonomic ganglionopathy (AAG) was made, and the management strategy shifted to first lowering the antibody burden by plasma exchanges and then instituting chronic anti-autoimmune treatment with rituximab and a low dose of cortiosteroid. The patient showed remarkable improvement.
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December 2017

A Prospective International Study on Adherence to Treatment in 305 Patients With Flaring SLE: Assessment by Drug Levels and Self-Administered Questionnaires.

Clin Pharmacol Ther 2018 06 9;103(6):1074-1082. Epub 2017 Nov 9.

University College London, Centre for Rheumatology, London, UK.

Nonadherence to treatment is a major cause of lupus flares. Hydroxychloroquine (HCQ), a major medication in systemic lupus erythematosus, has a long half-life and can be quantified by high-performance liquid chromatography. This international study evaluated nonadherence in 305 lupus patients with flares using drug levels (HCQ <200 ng/ml or undetectable desethylchloroquine), and self-administered questionnaires (MASRI <80% or MMAS-8 <6). Drug levels defined 18.4% of the patients as severely nonadherent. In multivariate analyses, younger age, nonuse of steroids, higher body mass index, and unemployment were associated with nonadherence by drug level. Questionnaires classified 39.9% of patients as nonadherent. Correlations between adherence measured by questionnaires, drug level, and physician assessment were moderate. Both methods probably measured two different patterns of nonadherence: self-administered questionnaires mostly captured relatively infrequently missed tablets, while drug levels identified severe nonadherence (i.e., interruption or erratic tablet intake). The frequency with which physicians miss nonadherence, together with underreporting by patients, suggests that therapeutic drug monitoring is useful in this setting. (Trial registration: ClinicalTrials.gov: NCT01509989.).
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http://dx.doi.org/10.1002/cpt.885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5858989PMC
June 2018

The interaction between anti-Ro/SSA and anti-La/SSB autoantibodies and anti-infectious antibodies in a wide spectrum of auto-immune diseases: another angle of the autoimmune mosaic.

Clin Exp Rheumatol 2017 Nov-Dec;35(6):929-935. Epub 2017 Jul 6.

Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center; Sackler Faculty of Medicine, Tel-Aviv University; and Incumbent of the Laura Schwarz-KipChair for Research of Autoimmune Diseases, Tel-Aviv University, Israel.

Objectives: The presence of anti-Ro/SSA and anti-La/SSB antibodies has been linked with autoimmunity in general and with several autoimmune diseases (AID) in particular. In the current study we evaluated these antibodies in a wide spectrum of AID as well as the links between them and anti-infectious antibodies.

Methods: We examined 2082 sera from patients with 16 different AID compared to 524 sera from geographically-matched healthy controls, for the presence and titres of anti-Ro/SSA and anti-La/SSB. All samples were also tested for a variety of anti-infectious agents' antibodies using the BioPlex 2200-immunoassay (Bio-Rad, USA).

Results: Anti-Ro/SSA was more prevalent, with significantly higher titre in 5 autoimmune diseases namely Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS) both primary and APS linked to SLE, systemic sclerosis (SSc) and primary biliary cirrhosis (PBC). Anti-La/SSB was more prevalent with higher titers in SS, SLE, APS linked to SLE and PBC. Prevalence, but not titers, of both antibodies were higher also in polymyositis (PM). Additionally, we found a correlation between anti-Ro/SSA antibodies and antibodies of the IgM and IgG subtypes directed at cytomegalovirus as well as IgG-antibodies directed at Epstein-Barr virus (EBV) and toxoplasma (p<0.001). Anti-La/SSB antibodies correlated with the presence of IgG antibodies against EBV early antigen (p<0.001).

Conclusions: In a large cohort of patients with autoimmune diseases we found an association between anti-Ro/SSA and anti-La/SSB antibodies and 6 autoimmune diseases, amongst which primary APS and PM. Additionally, we observed linkages between these autoantibodies and anti-infectious antibodies directed at Epstein-Barr virus, toxoplasma and cytomegalovirus. Our findings support the concept of interplay between infectious agents and autoimmunity, such as the plausibility of an infectious agent that trigger the immune system to produce specific antibodies which will later result in a unique group of AID.
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March 2018

Anti-BLyS Treatment of 36 Israeli Systemic Lupus Erythematosus Patients.

Isr Med Assoc J 2017 Jan;19(1):44-48

Department of Allergy and Clinical Immunology Unit, Sheba Medical Center, Tel Hashomer, Israel.

Background: Anti-BLyS treatment with the human belimumab monoclonal antibody was shown to be a safe and effective therapeutic modality in lupus patients with active disease (i.e., without significant neurological/renal involvement) despite standard treatment.

Objectives: To evaluate the "real-life" safety and efficacy of belimumab added to standard therapy in patents with active lupus in five Israeli medical centers.

Methods: We conducted a retrospective open-labeled study of 36 lupus patients who received belimumab monthly for at least 1 year in addition to standard treatment. Laboratory tests (C3/C4, anti dsDNA autoantibodies, chemistry, urinalysis and complete blood count) were done every 3-4 months. Adverse events were obtained from patients' medical records. Efficacy assessment by the treating physicians was defined as excellent, good/partial, or no response.

Results: The study group comprised 36 lupus patients (8 males, 28 females) with a mean age of 41.6 } 12.2 years. Belimumab was given for a mean period of 2.3 } 1.7 years (range 1-7). None of the patients discontinued belimumab due to adverse events. Four patients (11.1%) had an infection related to belimumab. Only 5 patients (13.9%) stopped taking belimumab due to lack of efficacy. The response was excellent in 25 patients (69.5%) and good/partial in the other 6 (16.6%). Concomitantly, serological response (reduction of C3/C4 and anti-dsDNA autoantibodies) was also observed. Moreover, following belimumab treatment, there was a significant reduction in the usage of corticosteroids (from 100% to 27.7%) and immunosuppressive agents (from 83.3% to 8.3%).

Conclusions: Belimumab, in addition to standard therapy, is a safe and effective treatment for active lupus patients.
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January 2017

Anti-mutated citrullinated vimentin antibodies in antiphospholipid syndrome: diagnostic value and relationship with clinical features.

Immunol Res 2017 04;65(2):524-531

Lupus Clinic, Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Viale del Policlinico 155, 00161, Rome, Italy.

Antiphospholipid antibodies (aPLs) are a heterogeneous group of autoantibodies essential for the diagnosis of antiphospholipid syndrome (APS) but do not predict clinical manifestations or disease progression. Hence, the co-presence of other antibodies may prove useful. Autoimmunity directed toward vimentin and other citrullinated peptides was established in rheumatoid arthritis (RA) and in other autoimmune conditions including systemic lupus erythematosus (SLE). We have previously described the presence of autoantibodies directed against vimentin/cardiolipin complex in patients with antiphospholipid syndrome (APS), but there are no data on the role of citrullinated vimentin in APS. Thus, we evaluated the prevalence and clinical significance of anti-MCV in APS patients. The study group consisted of 79 unselected outpatients with APS. Control groups included 25 patients with SLE, 30 patients with RA, and 20 healthy subjects age- and sex-matched. To detect anti-MCV, anti-vimentin, anti-vimentin/cardiolipin, and anti-CCP2 antibodies, commercial or homemade enzyme-linked immunosorbent assays (ELISA) were performed. Anti-MCV antibodies were found in a high percentage of APS patients (26.6%). A significant correlation between anti-MCV and anti-vimentin/cardiolipin serum levels was observed (p = 0.029). Moreover, vimentin reactivity was increased by its citrullination or conjugation with cardiolipin (p = 0.01 and p < 0.001, respectively). Interestingly, anti-MCV was found associated with the presence of arthritis (p = 0.011) and anti-vimentin/cardiolipin was highly specific for the presence of arterial or venous thrombosis in APS (p = 0.003 and p = 0.002, respectively). The detection of additional autoantibodies may contribute to clinical assessment of APS patients. Citrullination may occur in APS and play a role in the pathogenesis of this condition.

Key Points: •Anti-MCV antibodies can be found in APS patients and are associated with the presence of arthritis. •Anti-vimentin/cardiolipin is strongly associated with the presence of thrombosis (both arterial and venous). •Citrullination occurs in APS, participate in disease pathogenesis, and influence clinical picture.
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http://dx.doi.org/10.1007/s12026-017-8899-xDOI Listing
April 2017

Mindfulness-based group therapy for systemic lupus erythematosus: A first exploration of a promising mind-body intervention.

Complement Ther Clin Pract 2017 Feb 29;26:73-75. Epub 2016 Nov 29.

Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center, Ramat Gan, Israel; Incumbent of the Laura Schwarz-KipChair for Research of Autoimmune Diseases, Tel-Aviv University, Tel Aviv, Israel.

Psychological effects related to systemic lupus erythematosus (SLE) are tremendous. While a variety of psychological treatments have been applied to assist SLE patients, the effects of mindfulness practice were never documented in SLE. Mindfulness-based psychotherapy includes several techniques, including body-scan, breathing exercises, and full awareness during daily activities. In this case report, we present a first attempt at conducting mindfulness-based group therapy among SLE patients. Six female SLE patients participated in an 8-week program. Improvement was observed in several areas: patients' increased ability to differentiate between themselves and the disease; increased ability to accept, rather than to actively fight the fact that one must live with the disease; and decreased behavioral avoidance. These observations speak to the significant therapeutic potential of mindfulness practice among SLE patients. With its emphasis on acceptance of negative physical and emotional states, mindfulness practice is a promising treatment option, which needs to be further studied.
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http://dx.doi.org/10.1016/j.ctcp.2016.11.011DOI Listing
February 2017

A novel bedside test for ACPA: the CCPoint test is moving the laboratory to the rheumatologist's office.

Immunol Res 2017 02;65(1):363-368

Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center, Tel-Hashomer, 52621, Israel.

Rheumatoid Arthritis (RA) is an autoimmune destructive joint disease affecting 1 % of the general population. In recent years, the benefits of identifying RA at an early stage and initiating therapy before joint damage occurs have been acknowledged. An elevated anti-citrullinated peptide antibody (ACPA) level serves as a marker for the early diagnosis of RA. Often the diagnosis is delayed because conventional methods of antibody detection require referral to a specific laboratory. In the current study, we determined the diagnostic accuracy of a new lateral flow point-of-care kit available for ACPA detection in the rheumatologist office. The presence of ACPA was determined by the visually read, qualitative rapid CCPoint test (Euro-Diagnostica, Malmö, Sweden) compared to routinely used ELISA assays (Immunoscan CCPlus-Euro-Diagnostica, Sweden, and QuantLite CCP3-INOVA Diagnostics Inc., USA), in the sera of 184 patients: early RA(n = 38), established RA (n = 84), inflammatory arthritis(n = 34) and systemic lupus erythematosus (SLE) (n = 28). ACPA was detected in 18/38(47 %), 53/84(63 %), 2/34(6 %) and 2/28(7 %) of patients with early RA, established RA, inflammatory arthritis and SLE, respectively. The sensitivity and specificity, negative and positive predictive values of the CCPoint test were equivalent to the Immunoscan CCPlus and Quanta Lite CCP3 ELISA assays. Correlation between ACPA positive results detected in the different assays was 97 %, while negative agreement reached 98 %. Excellent correlation (100 %) was observed between CCPoint results obtained using capillary blood versus serum. CCPoint is a novel technology that allows for a rapid accurate analysis of ACPA and diagnosis during the patient's visit in the rheumatologist office.
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http://dx.doi.org/10.1007/s12026-016-8846-2DOI Listing
February 2017