Hypogammaglobulinemia Publications (7607)


Hypogammaglobulinemia Publications

Eur. J. Pharmacol.
Eur J Pharmacol 2017 Jan 14. Epub 2017 Jan 14.
Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Pattern recognition receptors (PRRs) recognize common microbial or host-derived macromolecules and have important roles in early activation and response of the immune system. Initiation of the innate immune response starts with the recognition of microbial structures called pathogen associated molecular patterns (PAMPs). Recognition of PAMPs is performed by germline-encoded receptors expressed mainly on immune cells termed pattern recognition receptors (PRRs). Read More

Several classes of pattern recognition receptors (PRRs) are involved in the pathogenesis of diseases, including Toll-like receptors (TLRs), C-type lectin receptors (CLRs), and Nod-like receptors (NLRs). Patients with primary immune deficiencies (PIDs) affecting TLR signaling can elucidate the importance of these proteins in the human immune system. Defects in interleukin-1 receptor-associated kinase-4 and myeloid differentiation factor 88 (MyD88) lead to susceptibility to infections with bacteria, while mutations in nuclear factor-κB essential modulator (NEMO) and other downstream mediators generally induce broader susceptibility to bacteria, viruses, and fungi. In contrast, TLR3 signaling defects are associated with susceptibility to herpes simplex virus type 1 encephalitis. Other PIDs induce functional alterations of TLR signaling pathways, such as common variable immunodeficiency in which plasmacytoid dendritic cell defects enhance defective responses of B cells to shared TLR agonists. Altered TLR responses to TLR2 and 4 agonists are seen in chronic granulomatous disease (CGD) and X-linked agammaglobulinemia (XLA). Enhanced TLR responses, meanwhile, are seen for TLRs 5 and 9 in CGD, TLRs 4, 7/8, and 9 in XLA, TLRs 2 and 4 in hyper IgE syndrome (HIES), and for most TLRs in adenosine deaminase deficiency. In this review we provide the reader with an update on the role of TLRs and downstream signaling pathways in PID disorders.

Asian Cardiovasc Thorac Ann
Asian Cardiovasc Thorac Ann 2017 Jan 1:218492316687934. Epub 2017 Jan 1.
1 Department of Respiratory Medicine, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India.

Good's syndrome or thymoma-associated immunodeficiency is a rare clinical entity that is often presumed to be common variable immunodeficiency, due to lack of awareness and recognition of this syndrome. This syndrome more often goes unrecognized if a thymoma is not detected. An appropriate immunological work-up that aids timely diagnosis and adequate therapy with antimicrobials and intravenous immunoglobulins are mandatory to prevent the long-term complications and mortality associated with this syndrome. Read More

We present the clinical and immunological profile of a young man with Good's syndrome that was initially presumed to be common variable immunodeficiency.

A disease-specific Health-related Quality of Life survey was developed for adult patients with antibody immune deficiency disorders as a tool (PADQOL-16) for assessing a patient's QOL issues and their relation to clinical status. Read More

Arthritis & rheumatology (Hoboken, N.J.)
Arthritis Rheumatol 2016 Dec 28. Epub 2016 Dec 28.
Vasculitis and Glomerulonephritis Center, Division of Nephrology, Massachusetts General Hospital, Boston, MA.

To evaluate the effect of rituximab on pathogenic autoantibodies and total immunoglobulin levels, and to identify serious adverse events, in patients with ANCA vasculitis treated with continuous B cell depletion.
We conducted a retrospective analysis of 239 patients with ANCA vasculitis treated with rituximab-induced continuous B cell depletion. Two treatment cohorts were analyzed: an induction group (n= 53) and a maintenance group (n=237). Read More

The change in ANCA titers and total immunoglobulin levels over time were evaluated using mixed-effects models. Risk factors for serious infections during maintenance were evaluated with Poisson regression.
During induction, IgG levels fell at a rate of 6% per month (95% CI, 4 to 8%), while ANCA levels declined at 47% per month (95% CI, 42 to 52%) and 48% per month (95% CI, 42 to 54%) for anti-MPO and anti-PR3 titers, respectively. During maintenance treatment, with a median duration of 2.4 (IQR, 1.5- 4.0) years, IgG levels declined at 0.6% per year (95% CI, -0.2 to 1.4%). New significant hypogammaglobulinemia (IgG < 400 mg/dL) during maintenance occurred in 4.6% of patients, all of whom were in the lowest baseline IgG quartile. Serious infections during maintenance occurred at a rate of 0.85 [95% CI, 0.66 to 1.1] per 10 patient years and were independently associated with an IgG level < 400mg/dL.
B cell targeted therapy causes a preferential decline in ANCA titers relative to total IgG levels. Despite prolonged maintenance therapy with rituximab, IgG levels remain essentially constant. Serious infections were rare. This article is protected by copyright. All rights reserved.

Eur. J. Cancer
Eur J Cancer 2017 Feb 24;72:103-111. Epub 2016 Dec 24.
Hematology and Clinical Immunology Unit, Department of Medicine, University of Padua, Italy; Venetian Institute of Molecular Medicine, Centro di Eccellenza per la Ricerca Biomedica Avanzata, Italy. Electronic address:
Korean J Pediatr
Korean J Pediatr 2016 Nov 30;59(Suppl 1):S49-S52. Epub 2016 Nov 30.
Department of Pediatrics, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea.; Pediatric Allergy and Respiratory Center, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea.

X-linked agammaglobulinemia (XLA) is a hereditary humoral immunodeficiency that results from Bruton's tyrosine kinase (BTK) gene mutations. These mutations cause defects in B-cell development, resulting in the virtual absence of these lymphocytes from the peripheral circulation. Consequently, this absence leads to a profound deficiency of lg all isotypes, and an increased susceptibility to encapsulated bacterial infections. Read More

A 15-month-old Korean boy presented with recurrent sinusitis and otitis media after 6 months of age, and had a family history of 2 maternal uncles with XLA. Laboratory tests revealed a profound deficiency of Ig isotypes, and a decreased count of CD19(+) B cells in the peripheral circulation. Based on his family history and our laboratory test results, he was diagnosed with XLA. We performed BTK gene analysis of peripheral blood samples obtained from family members to confirm the diagnosis. Mutational analysis revealed a novel hemizygous frameshift mutation (c.82delC, p.Arg28Alafs(*)5), in the BTK gene. His mother and maternal grandmother were heterozygous carriers of this mutation and his two maternal uncles were hemizygous at the same position. After XLA diagnosis, intravenous immunoglobulin (400 mg/kg, monthly) treatment was initiated; recurrent sinusitis and otitis media were subsequently brought under control. To our knowledge, this is the first reported case of a Korean pedigree with a novel mutation in the BTK gene.

Int. Arch. Allergy Immunol.
Int Arch Allergy Immunol 2016 24;171(3-4):180-193. Epub 2016 Dec 24.
Department of Laboratory Medicine, Imam Hassan Mojtaba Hospital, Alborz University of Medical Sciences, Karaj, Iran.

Primary antibody deficiencies (PADs) are the most common inherited primary immunodeficiencies in humans, characterized by hypogammaglobulinemia, an inability to produce specific antibodies, and recurrent infections mainly caused by encapsulated bacteria. However, it has been shown that inflammatory disorders, granulomatous lesions, lymphoproliferative diseases, cancer, and autoimmunity are associated with the various types of PAD. Both systemic and organ-specific autoimmune diseases could be attributed to B-cell defects in PAD patients. Read More

Immune thrombocytopenic purpura and autoimmune hemolytic anemia are the most common autoimmune disorders in this group of patients. The aim of this review is to describe the proposed mechanisms for autoimmunity and to review the literature with respect to the reported autoimmune disorders in each type of PAD.

In this study, we describe four patients from two unrelated families of different ethnicities with a primary immunodeficiency, predominantly manifesting as susceptibility to Epstein-Barr virus (EBV)-related diseases. Three patients presented with EBV-associated Hodgkin's lymphoma and hypogammaglobulinemia; one also had severe varicella infection. The fourth had viral encephalitis during infancy. Read More

Homozygous frameshift or in-frame deletions in CD70 in these patients abolished either CD70 surface expression or binding to its cognate receptor CD27. Blood lymphocyte numbers were normal, but the proportions of memory B cells and EBV-specific effector memory CD8(+) T cells were reduced. Furthermore, although T cell proliferation was normal, in vitro-generated EBV-specific cytotoxic T cell activity was reduced because of CD70 deficiency. This reflected impaired activation by, rather than effects during killing of, EBV-transformed B cells. Notably, expression of 2B4 and NKG2D, receptors implicated in controlling EBV infection, on memory CD8(+) T cells from CD70-deficient individuals was reduced, consistent with their impaired killing of EBV-infected cells. Thus, autosomal recessive CD70 deficiency is a novel cause of combined immunodeficiency and EBV-associated diseases, reminiscent of inherited CD27 deficiency. Overall, human CD70-CD27 interactions therefore play a nonredundant role in T and B cell-mediated immunity, especially for protection against EBV and humoral immunity.

Allergy Asthma Clin Immunol
Allergy Asthma Clin Immunol 2016 7;12:65. Epub 2016 Dec 7.
Department of Virology and Immunology, LabPLUS, Auckland City Hospital, Grafton, Auckland, 1148 New Zealand.

New Zealand is a developed geographically isolated country in the South Pacific with a population of 4.4 million. Genetic diagnosis is the standard of care for most patients with primary immunodeficiency disorders (PIDs). Read More

Since 2005, we have offered a comprehensive genetic testing service for PIDs and other immune-related disorders with a published sequence. Here we present results for this program, over the first decade, between 2005 and 2014.
We undertook testing in 228 index cases and 32 carriers during this time. The three most common test requests were for X-linked lymphoproliferative (XLP), tumour necrosis factor receptor associated periodic syndrome (TRAPS) and haemophagocytic lymphohistiocytosis (HLH). Of the 32 suspected XLP cases, positive diagnoses were established in only 2 patients. In contrast, genetic defects in 8 of 11 patients with suspected X-linked agammaglobulinemia (XLA) were confirmed. Most XLA patients were initially identified from absence of B cells. Overall, positive diagnoses were made in about 23% of all tests requested. The diagnostic rate was lowest for several conditions with locus heterogeneity.
Thorough clinical characterisation of patients can assist in prioritising which genes should be tested. The clinician-driven customised comprehensive genetic service has worked effectively for New Zealand. Next generation sequencing will play an increasing role in disorders with locus heterogeneity.