Publications by authors named "Fayhan Alroqi"

15 Publications

  • Page 1 of 1

Seroprevalence of SARS-CoV-2 among high-risk healthcare workers in a MERS-CoV endemic area.

J Infect Public Health 2021 Sep 25;14(9):1268-1273. Epub 2021 Aug 25.

College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia; King Abdullah International Medical Research Centre (KAIMRC), Ministry of National Guard Health Affairs (MNGHA), Riyadh, Saudi Arabia. Electronic address:

Introduction: Healthcare workers (HCWs) in Saudi Arabia are a unique population who have had exposures to the Middle East Respiratory Syndrome coronavirus (MERS-CoV) and Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It follows that HCWs from this country could have pre-existingMERS-CoV antibodies that may either protect from coronavirus disease 2019 (COVID-19) infection or cause false SARS-CoV-2 seropositive results. In this article, we report the seroprevalence of MERS-CoV and SARS-CoV-2 among high-risk healthcare workers in Riyadh city, Saudi Arabia.

Methods: This is a cross-sectional study enrolling 420 high-risk HCWs who are physically in contact with COVID-19 patients in three tertiary hospitals in Riyadh city. The participants were recruited between the 1st of July to the end of December 2020. A 3 ml of the venous blood samples were collected and tested for the presence of IgG antibodies against the spike proteins of SARS-CoV-2 and MERS-CoV using enzyme-linked immunosorbent assay (ELISA).

Results: The overall prevalence of SARS-CoV-2 in high-risk HCWs was 14.8% based on SARS-CoV-2 IgG testing while only 7.4% were positive by Polymerase Chain Reaction (PCR) for viral RNA. Most of the SARS-CoV-2 seropositive HCWs had symptoms and the most frequent symptoms were body aches, fever, cough, loss of smell and taste, and headache. The seroprevalence of MERS-CoV IgG was 1% (4 participants) and only one participant had dual seropositivity against MERS-CoV and SARS-CoV-2. Three MERS-CoV positive samples (75%) turned to be negative after using in-house ELISA and none of the MERS-CoV seropositive samples had detectable neutralization activity.

Conclusion: Our SARS-CoV-2 seroprevalence results were higher than reported regional seroprevalence studies. This finding was expected and similar to other international findings that targeted high-risk HCWs. Our results provide evidence that the SARS-CoV-2- seropositivity in Saudi Arabia similar to other countries was due to exposure to SARS-CoV-2 rather than MERS-CoV antibody.
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http://dx.doi.org/10.1016/j.jiph.2021.08.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386093PMC
September 2021

Nationwide Seroprevalence of SARS-CoV-2 in Saudi Arabia.

J Infect Public Health 2021 Jul 24;14(7):832-838. Epub 2021 Apr 24.

King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.

Background: Estimated seroprevalence of Coronavirus Infectious Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is a critical evidence for a better evaluation of the virus spread and monitoring the progress of COVID-19 pandemic in a population. In the Kingdom of Saudi Arabia (KSA), SARS-CoV-2 seroprevalence has been reported in specific regions, but an extensive nationwide study has not been reported. Here, we report a nationwide study to determine the prevalence of SARS-CoV-2 in the population of KSA during the pandemic, using serum samples from healthy blood donors, non-COVID patients and healthcare workers (HCWs) in six different regions of the kingdom, with addition samples from COVID-19 patients.

Methods: A total of 11,703 serum samples were collected from different regions of the KSA including; 5395 samples from residual healthy blood donors (D); 5877 samples from non-COVID patients collected through residual sera at clinical biochemistry labs from non-COVID patients (P); and 400 samples from consented HCWs. To determine the seroprevalence of SARS-CoV-2, all serum samples, in addition to positive control sera from RT-PCR confirmed COVID-19 patients, were subjected to in-house ELISA with a sample pooling strategy, which was further validated by testing individual samples that make up some of the pools, with a statistical estimation method to report seroprevalence estimates.

Results: Overall (combining D and P groups) seroprevalence estimate was around 11% in Saudi Arabia; and was 5.1% (Riyadh), 1.5% (Jazan), 18.4% (Qassim), 20.8% (Hail), 14.7% (ER; Alahsa), and 18.8% in Makkah. Makkah samples were only D group and had a rate of 24.4% and 12.8% in the cities of Makkah and Jeddah, respectively. The seroprevalence in Saudi Arabia across the sampled areas would be 12 times the reported COVID-19 infection rate. Among HCWs, 7.5% (4.95-10.16 CI 95%) had reactive antibodies to SARS-CoV-2 without reporting any previously confirmed infection. This was higher in HCWs with hypertension. The study also presents the demographics and prevalence of co-morbidities in HCWs and subset of non-COVID-19 population.

Interpretation: Our study estimates the overall national serological prevalence of COVID-19 in Saudi Arabia to be 11%, with an apparent disparity between regions. This indicates the prevalence of asymptomatic or mild unreported COVID-19 cases.
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http://dx.doi.org/10.1016/j.jiph.2021.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188888PMC
July 2021

Inherited deficiency of stress granule ZNFX1 in patients with monocytosis and mycobacterial disease.

Proc Natl Acad Sci U S A 2021 Apr;118(15)

Pediatric Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran 19569-44413, Iran.

Human inborn errors of IFN-γ underlie mycobacterial disease, due to insufficient IFN-γ production by lymphoid cells, impaired myeloid cell responses to this cytokine, or both. We report four patients from two unrelated kindreds with intermittent monocytosis and mycobacterial disease, including bacillus Calmette-Guérin-osis and disseminated tuberculosis, and without any known inborn error of IFN-γ. The patients are homozygous for variants (p.S959* and p.E1606Rfs*10) predicted to be loss of function (pLOF). There are no subjects homozygous for pLOF variants in public databases. ZNFX1 is a conserved and broadly expressed helicase, but its biology remains largely unknown. It is thought to act as a viral double-stranded RNA sensor in mice, but these patients do not suffer from severe viral illnesses. We analyze its subcellular localization upon overexpression in A549 and HeLa cell lines and upon stimulation of THP1 and fibroblastic cell lines. We find that this cytoplasmic protein can be recruited to or even induce stress granules. The endogenous ZNFX1 protein in cell lines of the patient homozygous for the p.E1606Rfs*10 variant is truncated, whereas ZNFX1 expression is abolished in cell lines from the patients with the p.S959* variant. Lymphocyte subsets are present at normal frequencies in these patients and produce IFN-γ normally. The hematopoietic and nonhematopoietic cells of the patients tested respond normally to IFN-γ. Our results indicate that human ZNFX1 is associated with stress granules and essential for both monocyte homeostasis and protective immunity to mycobacteria.
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http://dx.doi.org/10.1073/pnas.2102804118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053974PMC
April 2021

Classical and Counter-Regulatory Renin-Angiotensin System: Potential Key Roles in COVID-19 Pathophysiology.

CJC Open 2021 Aug 15;3(8):1060-1074. Epub 2021 Apr 15.

King Abdullah International Medical Research Centre, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.

In the current COVID-19 pandemic, severe acute respiratory syndrome coronavirus 2 uses angiotensin-converting enzyme-2 (ACE-2) receptors for cell entry, leading to ACE-2 dysfunction and downregulation, which disturb the balance between the classical and counter-regulatory renin-angiotensin system (RAS) in favor of the classical RAS. RAS dysregulation is one of the major characteristics of several cardiovascular diseases; thus, adjustment of this system is the main therapeutic target. RAS inhibitors-particularly angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs)-are commonly used for treatment of hypertension and cardiovascular disease. Patients with cardiovascular diseases are the group most commonly seen among those with COVID-19 comorbidity. At the beginning of this pandemic, a dilemma occurred regarding the use of ACEIs and ARBs, potentially aggravating cardiovascular and pulmonary dysfunction in COVID-19 patients. Urgent clinical trials from different countries and hospitals reported that there is no association between RAS inhibitor treatment and COVID-19 infection or comorbidity complication. Nevertheless, the disturbance of the RAS that is associated with COVID-19 infection and the potential treatment targeting this area have yet to be resolved. In this review, the link between the dysregulation of classical RAS and counter-regulatory RAS activities in COVID-19 patients with cardiovascular metabolic diseases is investigated. In addition, the latest findings based on ACEI and ARB administration and ACE-2 availability in relation to COVID-19, which may provide a better understanding of the RAS contribution to COVID-19 pathology, are discussed, as they are of the utmost importance amid the current pandemic.
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http://dx.doi.org/10.1016/j.cjco.2021.04.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046706PMC
August 2021

NCKAP1L defects lead to a novel syndrome combining immunodeficiency, lymphoproliferation, and hyperinflammation.

J Exp Med 2020 12;217(12)

Department of Pediatrics, King Abdulaziz Medical City, King Abdullah Specialized Children's Hospital, Riyadh, Saudi Arabia.

The Nck-associated protein 1-like (NCKAP1L) gene, alternatively called hematopoietic protein 1 (HEM-1), encodes a hematopoietic lineage-specific regulator of the actin cytoskeleton. Nckap1l-deficient mice have anomalies in lymphocyte development, phagocytosis, and neutrophil migration. Here we report, for the first time, NCKAP1L deficiency cases in humans. In two unrelated patients of Middle Eastern origin, recessive mutations in NCKAP1L abolishing protein expression led to immunodeficiency, lymphoproliferation, and hyperinflammation with features of hemophagocytic lymphohistiocytosis. Immunophenotyping showed an inverted CD4/CD8 ratio with a major shift of both CD4+ and CD8+ cells toward memory compartments, in line with combined RNA-seq/proteomics analyses revealing a T cell exhaustion signature. Consistent with the core function of NCKAP1L in the reorganization of the actin cytoskeleton, patients' T cells displayed impaired early activation, immune synapse morphology, and leading edge formation. Moreover, knockdown of nckap1l in zebrafish led to defects in neutrophil migration. Hence, NCKAP1L mutations lead to broad immune dysregulation in humans, which could be classified within actinopathies.
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http://dx.doi.org/10.1084/jem.20192275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526481PMC
December 2020

Homozygous truncating NEK10 mutation, associated with primary ciliary dyskinesia: a case report.

BMC Pulm Med 2020 May 15;20(1):141. Epub 2020 May 15.

Medical Genetics Division, Department of Pediatrics, King Abdullah specialized Children's Hospital, King Abdulaziz Medical City, P. O Box 22490, Riyadh, 11426, Saudi Arabia.

Background: Primary Ciliary Dyskinesia (PCD) is also known as immotile-cilia syndrome, an autosomal recessive disorder of ciliary function, leading to mucus retention in the respiratory system in childhood. Our knowledge in the pathophysiological aspect of this devastating disorder is increasing with the advancement of genetic and molecular testing.

Case Presentation: Here in, we report two siblings with a classical clinical and radiological presentation of PCD. Using whole exome sequencing we identified a homozygous truncating variant (c.3402 T > A); p.(Tyr1134*) in the NEK10 gene. Western bolt analysis revealed a decrease in the expression of NEK10 protein in the patient cells.

Conclusions: NEK10 plays a central role in the post-mitotic process of cilia assembly, regulating ciliary length and functions during physiological and pathological status. This study highlights the challenges of identifying disease-causing variants for a highly heterogeneous disorder and reports on the identification of a novel variant in NEK10 which recently associated with PCD.
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http://dx.doi.org/10.1186/s12890-020-1175-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229615PMC
May 2020

Successful hematopoietic stem cell transplant in leukocyte adhesion deficiency type III presenting primarily as malignant infantile osteopetrosis.

Clin Immunol 2020 04 21;213:108365. Epub 2020 Feb 21.

Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

Leukocyte adhesion deficiency type III (LAD-III) is caused by mutations in FERMT3 that encodes Kindlin-3 which regulates integrins activation. LAD-III predisposes to infections and bleeding. Osteopetrosis was reported in some cases. We report three patients who presented as malignant infantile osteopetrosis. One had recurrent infections and none had bleeding. Exome sequencing revealed a novel homozygous mutation in FERMT3 c.1555C > T (p.Gln519Ter). Two patients underwent successful hematopoietic stem cell transplant (HSCT) from matched siblings with resolution of osteopetrosis. The third patient died secondary to sepsis prior to HSCT. Our results support early HSCT in LAD-III prior to the occurrence of life-threatening complications.
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http://dx.doi.org/10.1016/j.clim.2020.108365DOI Listing
April 2020

Hypomorphic variants in AK2 reveal the contribution of mitochondrial function to B-cell activation.

J Allergy Clin Immunol 2020 07 17;146(1):192-202. Epub 2019 Dec 17.

Pediatrics Department, Hotel Dieu de France University Hospital, Saint Joseph University, Beirut, Lebanon.

Background: The gene AK2 encodes the phosphotransferase adenylate kinase 2 (AK2). Human variants in AK2 cause reticular dysgenesis, a severe combined immunodeficiency with agranulocytosis, lymphopenia, and sensorineural deafness that requires hematopoietic stem cell transplantation for survival.

Objective: We investigated the mechanisms underlying recurrent sinopulmonary infections and hypogammaglobulinemia in 15 patients, ranging from 3 to 34 years of age, from 9 kindreds. Only 2 patients, both of whom had mildly impaired T-cell proliferation, each had a single clinically significant opportunistic infection.

Methods: Patient cells were studied with next-generation DNA sequencing, tandem mass spectrometry, and assays of lymphocyte and mitochondrial function.

Results: We identified 2 different homozygous variants in AK2. AK2 and AK2 permit residual protein expression, enzymatic activity, and normal numbers of neutrophils and lymphocytes. All but 1 patient had intact hearing. The patients' B cells had severely impaired proliferation and in vitro immunoglobulin secretion. With activation, the patients' B cells exhibited defective mitochondrial respiration and impaired regulation of mitochondrial membrane potential and quality. Although activated T cells from the patients with opportunistic infections demonstrated impaired mitochondrial function, the mitochondrial quality in T cells was preserved. Consistent with the capacity of activated T cells to utilize nonmitochondrial metabolism, these findings revealed a less strict cellular dependence of T-cell function on AK2 activity. Chemical inhibition of ATP synthesis in control T and B cells similarly demonstrated the greater dependency of B cells on mitochondrial function.

Conclusions: Our patients demonstrate the in vivo sequelae of the cell-specific requirements for the functions of AK2 and mitochondria, particularly in B-cell activation and antibody production.
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http://dx.doi.org/10.1016/j.jaci.2019.12.004DOI Listing
July 2020

Duplicate skin prick testing in the assessment of food allergy.

J Allergy Clin Immunol Pract 2019 Feb 1;7(2):675-677. Epub 2018 Aug 1.

Department of Allergy/Immunology, Boston Children's Hospital, Boston, Mass; Department of Pediatrics, Harvard Medical School, Boston, Mass. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2018.07.024DOI Listing
February 2019

DOCK8 Deficiency Presenting as an IPEX-Like Disorder.

J Clin Immunol 2017 Nov 23;37(8):811-819. Epub 2017 Oct 23.

Division of Immunology, Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Karp Family Building, Room 10-214. 1 Blackfan Street, Boston, MA, 02115, USA.

Purpose: The dedicator of cytokinesis 8 (DOCK8) deficiency is an autosomal recessive-combined immunodeficiency whose clinical spectra include recurrent infections, autoimmunity, malignancies, elevated serum IgE, eczema, and food allergies. Here, we report on patients with loss of function DOCK8 mutations with profound immune dysregulation suggestive of an immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX)-like disorder.

Methods: Immunophenotyping of lymphocyte subpopulations and analysis of DOCK8 protein expression were evaluated by flow cytometry. T regulatory (T) cells were isolated by cell sorting, and their suppressive activity was analyzed by flow cytometry. Gene mutational analysis was performed by whole-exome and Sanger sequencing.

Results: Patient 1 (P1) presented at 10 months of age with chronic severe diarrhea and active colitis in the absence of an infectious trigger, severe eczema with elevated serum IgE, and autoimmune hemolytic anemia, suggestive of an IPEX-related disorder. Whole-exome sequencing revealed a homozygous nonsense mutation in DOCK8 at the DOCK-homology region (DHR)-1 (c.1498C>T; p. R500X). Patient P2, a cousin of P1 who carries the same DOCK8 nonsense mutation, presented with eczema and recurrent ear infections in early infancy, and she developed persistent diarrhea by 3 years of age. Patient P3 presented with lymphoproliferation, severe eczema with allergic dysregulation, and chronic diarrhea with colitis. She harbored a homozygous loss of function DOCK8 mutation (c.2402 -1G→A). T cell function was severely compromised by both DOCK8 mutations.

Conclusion: DOCK8 deficiency may present severe immune dysregulation with features that may overlap with those of IPEX and other IPEX-like disorders.
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http://dx.doi.org/10.1007/s10875-017-0451-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5691358PMC
November 2017

Exaggerated follicular helper T-cell responses in patients with LRBA deficiency caused by failure of CTLA4-mediated regulation.

J Allergy Clin Immunol 2018 03 7;141(3):1050-1059.e10. Epub 2017 Jun 7.

Division of Immunology, Boston Children's Hospital, and the Department of Pediatrics, Harvard Medical School, Boston, Mass. Electronic address:

Background: LPS-responsive beige-like anchor protein (LRBA) and cytotoxic T lymphocyte-associated antigen 4 (CTLA4) deficiencies give rise to overlapping phenotypes of immune dysregulation and autoimmunity, with dramatically increased frequencies of circulating follicular helper T (cT) cells.

Objective: We sought to determine the mechanisms of cT cell dysregulation in patients with LRBA deficiency and the utility of monitoring cT cells as a correlate of clinical response to CTLA4-Ig therapy.

Methods: cT cells and other lymphocyte subpopulations were characterized. Functional analyses included in vitro follicular helper T (T) cell differentiation and cT/naive B-cell cocultures. Serum soluble IL-2 receptor α chain levels and in vitro immunoglobulin production by cultured B cells were quantified by using ELISA.

Results: cT cell frequencies in patients with LRBA or CTLA4 deficiency sharply decreased with CTLA4-Ig therapy in parallel with other markers of immune dysregulation, including soluble IL-2 receptor α chain, CD45ROCD4 effector T cells, and autoantibodies, and this was predictive of favorable clinical responses. cT cells in patients with LRBA deficiency were biased toward a T1-like cell phenotype, which was partially reversed by CTLA4-Ig therapy. LRBA-sufficient but not LRBA-deficient regulatory T cells suppressed in vitro T cell differentiation in a CTLA4-dependent manner. LRBA-deficient T cells supported in vitro antibody production by naive LRBA-sufficient B cells.

Conclusions: cT cell dysregulation in patients with LRBA deficiency reflects impaired control of T cell differentiation because of profoundly decreased CTLA4 expression on regulatory T cells and probably contributes to autoimmunity in patients with this disease. Serial monitoring of cT cell frequencies is highly useful in gauging the clinical response of LRBA-deficient patients to CTLA4-Ig therapy.
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http://dx.doi.org/10.1016/j.jaci.2017.05.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5743769PMC
March 2018

Ruxolitinib reverses dysregulated T helper cell responses and controls autoimmunity caused by a novel signal transducer and activator of transcription 1 (STAT1) gain-of-function mutation.

J Allergy Clin Immunol 2017 May 27;139(5):1629-1640.e2. Epub 2017 Jan 27.

Division of Immunology, Boston Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, Mass.

Background: Gain-of-function (GOF) mutations in the human signal transducer and activator of transcription 1 (STAT1) manifest in immunodeficiency and autoimmunity with impaired T17 cell differentiation and exaggerated responsiveness to type I and II interferons. Allogeneic bone marrow transplantation has been attempted in severely affected patients, but outcomes have been poor.

Objective: We sought to define the effect of increased STAT1 activity on T helper cell polarization and to investigate the therapeutic potential of ruxolitinib in treating autoimmunity secondary to STAT1 GOF mutations.

Methods: We used in vitro polarization assays, as well as phenotypic and functional analysis of STAT1-mutated patient cells.

Results: We report a child with a novel mutation in the linker domain of STAT1 who had life-threatening autoimmune cytopenias and chronic mucocutaneous candidiasis. Naive lymphocytes from the affected patient displayed increased T1 and follicular T helper cell and suppressed T17 cell responses. The mutation augmented cytokine-induced STAT1 phosphorylation without affecting dephosphorylation kinetics. Treatment with the Janus kinase 1/2 inhibitor ruxolitinib reduced hyperresponsiveness to type I and II interferons, normalized T1 and follicular T helper cell responses, improved T17 differentiation, cured mucocutaneous candidiasis, and maintained remission of immune-mediated cytopenias.

Conclusions: Autoimmunity and infection caused by STAT1 GOF mutations are the result of dysregulated T helper cell responses. Janus kinase inhibitor therapy could represent an effective targeted treatment for long-term disease control in severely affected patients for whom hematopoietic stem cell transplantation is not available.
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http://dx.doi.org/10.1016/j.jaci.2016.11.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482293PMC
May 2017

Severe Early-Onset Combined Immunodeficiency due to Heterozygous Gain-of-Function Mutations in STAT1.

J Clin Immunol 2016 10 5;36(7):641-8. Epub 2016 Jul 5.

Division of Pediatric Allergy/Immunology, Marmara University, Fevzi Çakmak Mah. No: 41, Pendik, Istanbul, Turkey.

Purpose: Loss and gain-of-function (GOF) mutations in human signal transducer and activator of transcription 1 (STAT1) lead to distinct phenotypes. Although recurrent infections are common to both types of STAT1 mutations, GOF mutations are distinguished by chronic mucocutaneous candidiasis and autoimmunity. However, the clinical spectra of STAT1 GOF mutations continue to expand. We here describe two patients with STAT1 GOF mutations presenting early in life with combined immunodeficiency (CID).

Methods: Clinical data and laboratory findings including immunophenotyping, level of interferon (IFN)-γ/IL-17(+) T cells, interferon-induced STAT1 phosphorylation, and JAK inhibitor assays were evaluated. Sequencing of STAT1 gene was performed by Sanger sequencer.

Results: Patient 1 (P1) had persistent oral candidiasis and cytomegalovirus (CMV) infection since 2 months of age and later developed cavitary lung lesions due to Mycobacterium tuberculosis. Patient 2 (P2) presented with oral candidiasis and recurrent pneumonia at 4 months of age and subsequently developed CMV pneumonitis. Both patients suffered heterozygous missense mutations in STAT1, leading to deleterious amino acid substitutions in the DNA binding domain (P1: c.1154C > T; p.T385M; P2. c.971G > T; p.C324F). Circulating CD4(+) T cells of both patients exhibited increased interferon-γ and decreased IL-17 expression as compared to controls. They also exhibited increased IFN-β and -γ-induced STAT1 phosphorylation that was reversed upon treatment with the JAK kinase inhibitor ruxolitinib.

Conclusion: STAT1 GOF mutations may present early in life with CID, consistent with the clinical heterogeneity of the disease. JAK kinase inhibitors may potentially be useful in some patients as adjunct therapy pending definitive treatment with bone marrow transplantation.
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http://dx.doi.org/10.1007/s10875-016-0312-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5556363PMC
October 2016

T Regulatory Cell Biology in Health and Disease.

Curr Allergy Asthma Rep 2016 Apr;16(4):27

Division of Immunology, Boston Children's Hospital, Karp Family Building, Room 10-214. 1 Blackfan Street, Boston, MA, 02115, USA.

Regulatory T (Treg) cells that express the transcription factor forkhead box protein P3 (FOXP3) play an essential role in enforcing immune tolerance to self tissues, regulating host-commensal flora interaction, and facilitating tissue repair. Their deficiency and/or dysfunction trigger unbridled autoimmunity and inflammation. A growing number of monogenic defects have been recognized that adversely impact Treg cell development, differentiation, and/or function, leading to heritable diseases of immune dysregulation and autoimmunity. In this article, we review recent insights into Treg cell biology and function, with particular attention to lessons learned from newly recognized clinical disorders of Treg cell deficiency.
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http://dx.doi.org/10.1007/s11882-016-0606-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5218767PMC
April 2016

A novel mutation in the POLE2 gene causing combined immunodeficiency.

J Allergy Clin Immunol 2016 Feb 11;137(2):635-638.e1. Epub 2015 Sep 11.

Department of Laboratory Medicine, Boston Children's Hospital, Boston, Mass; Department of Laboratory Medicine, Joint Program in Transfusion Medicine, Boston Children's Hospital, Boston, Mass; Department of Pathology, Harvard Medical School, Boston, Mass. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2015.06.049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747780PMC
February 2016
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