Research

Primary Antibody Deficiency in a Tertiary Referral Hospital: A 30-Year Experiment.

J Investig Allergol Clin Immunol. 2015;25(6):416-25

Authors: Mohammadinejad P, Pourhamdi S, Abolhassani H, Mirminachi B, Havaei A, Masoom SN, Sadeghi B, Ghajar A, Afarideh M, Parvaneh N, Mirsaeed-Ghazi B, Movahedi M, Gharagozlou M, Chavoushzadeh Z, Mahdaviani A, Zandieh F, Sherkat R, Sadeghi-Shabestari M, Faridhosseini R, Jabbari-Azad F, Ahanchian H, Zandkarimi M, Cherghi T, Fayezi A, Mohammadzadeh I, Amin R, Aleyasin S, Moghtaderi M, Ghaffari J, Bemanian M, Shafiei A, Kalantari N, Ahmadiafshar A, Khazaei HA, Mohammadi J, Nabavi M, Rezaei N, Aghamohammadi A

Abstract
BACKGROUND: Primary antibody deficiency (PAD) is the most common group of primary immunodeficiency disorders (PID), with a broad spectrum of clinical features ranging from severe and recurrent infections to asymptomatic disease.
OBJECTIVES: The current study was performed to evaluate and compare demographic and clinical data in the most common types of PAD.
MATERIALS AND METHODS: We performed a retrospective review of the medical records of all PAD patients with a confirmed diagnosis of common variable immunodeficiency (CVID), hyper IgM syndrome (HIgM), selective IgA deficiency (SIgAD), and X-linked agammaglobulinemia (XLA) who were diagnosed during the last 30 years at the Children’s Medical Center, Tehran, Iran.
RESULTS: A total number of 280 cases of PAD (125 CVID, 32 HIgM, 63 SIgAD, and 60 XLA) were enrolled in the study. The median (range) age at the onset of disease in CVID, HIgM, SIgAD, and XLA was 2 (0-46), 0.91 (0-9), 1 (0-26), and 1 (0-10) years, respectively. Gastrointestinal infections were more prevalent in CVID patients, as were central nervous system infections in XLA patients. Autoimmune complications were more prevalent in HIgM patients, malignancies in CVID patients, and allergies in SIgAD patients. The mortality rate for CVID, HIgM, and XLA was 27.2%, 28.1%, and 25%, respectively. No deaths were reported in SIgAD patients.
CONCLUSIONS: SIgAD patients had the best prognosis. While all PAD patients should be monitored for infectious complications, special attention should be paid to the finding of malignancy and autoimmune disorders in CVID and HIgM patients, respectively.

PMID: 26817138 [PubMed – in process]

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How effective are the 6 European Society of Immunodeficiency warning signs for primary immunodeficiency disease?

Ann Allergy Asthma Immunol. 2016 Feb;116(2):151-155.e1

Authors: Arslan S, Ucar R, Caliskaner AZ, Reisli I, Guner SN, Sayar EH, Baloglu I

Abstract
BACKGROUND: The European Society of Immunodeficiency (ESID) developed 6 warning signs to promote the awareness of adult primary immunodeficiency disease (PID).
OBJECTIVE: To screen adult patients for the presence of PID using these 6 warning signs to determine the effectiveness of this protocol.
METHODS: Questions related to the ESID warning signs for adult PID were added to the standard outpatient clinic file system and asked of 3,510 patients who were admitted to our clinic for any reason. Patients with signs and/or suspicion of PID based on their medical history underwent immunologic investigation.
RESULTS: In total, 24 patients were diagnosed as having a PID. The most common reason that patients with PID were admitted was frequent infection (n=18 [75%]), and the most common PID subgroup was common variable immunodeficiency (n=12 [50%]). Twenty patients with PID had at least one positive finding according to the ESID warning signs. Two patients with gastrointestinal concerns and 2 with dermatologic symptoms were also diagnosed as having a PID, although they did not have any of the ESID warning signs.
CONCLUSION: The ESID warning signs do not specify the need for symptoms to diagnose a PIDs and do not include a comprehensive list of all signs and symptoms of PIDs. As a result, more than infection-centric questions are needed to identify adult patients with immunodeficiencies.

PMID: 26815708 [PubMed – as supplied by publisher]

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Related Articles

Multiple malignancies in a female patient with common variable immunodeficiency syndrome.

Singapore Med J. 2014 Oct;55(10):e162-4

Authors: Todorovic M, Balint B, Andjelic B, Mihaljevic B

Abstract
We herein present the case of a 55-year-old woman with a previous history of malignancies–uterine adenocarcinoma, basal cell carcinoma (which occurred twice consecutively), recurrent respiratory infections due to common variable immunodeficiency (CVID), and systemic granulomatous disease diagnosed at a later age. The patient suffered from diffuse large B cell lymphoma (DLBCL), which was successfully treated with R-CHOP chemotherapy, and continued with immunoglobulin supplementation. The patient was free of lymphoma and infectious complications for over 20 months despite her persistent immunodeficiency, but eventually developed colorectal adenocarcinoma. To the best of our knowledge, this is the first reported case of CVID associated with multiple solid tumours and DLBCL.

PMID: 25631905 [PubMed – indexed for MEDLINE]

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Long-term follow-up of ninety eight Iranian patients with primary immune deficiency in a single tertiary centre.

Allergol Immunopathol (Madr). 2016 Jan 20;

Authors: Nabavi M, Arshi S, Bemanian MH, Aghamohammadi A, Mansouri D, Hedayat M, Nateghian A, Noorbakhsh S, Ehsanipour F, Faranoush M, Shakeri R, Mesdaghi M, Taghvaei B, Ghalebaghi B, Babaie D, Bahrami A, Fallahpour M, Esmaeilzadeh H, Ali Hamidieh A, Rekabi M, Ahmadian J, Eslami N, Shokri S, Afshar M, Jalali F, Akbarpour N, Molatefi R, Rezaei N

Abstract
PURPOSE: The aim was to describe the clinical manifestations, complications and long-term outcome of a cohort of Iranian patients with primary immune deficiency (PID).
METHOD: We retrospectively studied the demographic, clinical and immunological characteristics of the PID patients in a single tertiary centre, from January 1989 to July 2014. The patients were classified according to the International Union of Immunological Societies Expert Committee on PID.
RESULTS: 98 patients were diagnosed with and followed-up for 15 disorders. The mean age at onset and diagnosis and the diagnostic delay were 8±10, 14.2±13.1 and 6.1±7 years, respectively. Parental consanguinity rate was 57%. Predominantly Antibody Deficiency was the most common diagnosis (n=63), followed by congenital defects of phagocytes (n=16), combined immunodeficiencies (n=12), well defined syndromes (n=4) and defects in innate immunity (n=3). Recurrent sinopulmonary infection was the most common presentation. Active infections were treated appropriately, in addition to prophylactic therapy with IVIG and antimicrobials. Not all the patients were compliant with prophylactic regimens due to cost and unavailability. One SCID patient underwent successful bone marrow transplantation. The total mortality rate was 19% during the follow-up period (7.8±7.6 years). The mean age of living patients at the time of study was 23±11.7 years.
CONCLUSIONS: Physicians awareness of PID has been rising dramatically in Iran, ensuring an increasing number of patients being diagnosed and treated. More effective treatment services, including health insurance coverage and drug availability are needed to improve the outcome of PID patients.

PMID: 26803694 [PubMed – as supplied by publisher]

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Recruitment of A20 by the C-terminal domain of NEMO suppresses NF-κB activation and autoinflammatory disease.

Proc Natl Acad Sci U S A. 2016 Jan 22;

Authors: Zilberman-Rudenko J, Shawver LM, Wessel AW, Luo Y, Pelletier M, Tsai WL, Lee Y, Vonortas S, Cheng L, Ashwell JD, Orange JS, Siegel RM, Hanson EP

Abstract
Receptor-induced NF-κB activation is controlled by NEMO, the NF-κB essential modulator. Hypomorphic NEMO mutations result in X-linked ectodermal dysplasia with anhidrosis and immunodeficiency, also referred to as NEMO syndrome. Here we describe a distinct group of patients with NEMO C-terminal deletion (ΔCT-NEMO) mutations. Individuals harboring these mutations develop inflammatory skin and intestinal disease in addition to ectodermal dysplasia with anhidrosis and immunodeficiency. Both primary cells from these patients, as well as reconstituted cell lines with this deletion, exhibited increased IκB kinase (IKK) activity and production of proinflammatory cytokines. Unlike previously described loss-of-function mutations, ΔCT-NEMO mutants promoted increased NF-κB activation in response to TNF and Toll-like receptor stimulation. Investigation of the underlying mechanisms revealed impaired interactions with A20, a negative regulator of NF-κB activation, leading to prolonged accumulation of K63-ubiquitinated RIP within the TNFR1 signaling complex. Recruitment of A20 to the C-terminal domain of NEMO represents a novel mechanism limiting NF-κB activation by NEMO, and its absence results in autoinflammatory disease.

PMID: 26802121 [PubMed – as supplied by publisher]

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F-actin remodeling defects as revealed in primary immunodeficiency disorders.

Clin Immunol. 2016 Jan 20;

Authors: Janssen WJ, Geluk HC, Boes M

Abstract
Primary immunodeficiencies (PIDs) are a heterogeneous group of immune-related diseases. PIDs develop due to defects in gene-products that have consequences to immune cell function. A number of PID-proteins is involved in the remodeling of filamentous actin (f-actin) to support the generation of a contact zone between the antigen-specific T cell and antigen presenting cell (APC): the immunological synapse (IS). IS formation is the first step towards T-cell activation and essential for clonal expansion and acquisition of effector function. We here evaluated PIDs in which aberrant f-actin-driven IS formation may contribute to the PID disease phenotypes as seen in patients. We review examples of such contributions to PID phenotypes from literature, and highlight cases in which PID-proteins were evaluated for a role in f-actin polymerization and IS formation. We conclude with the proposition that patient groups might benefit from stratifying them in distinct functional groups in regard to their f-actin remodeling phenotypes in lymphocytes.

PMID: 26802313 [PubMed – as supplied by publisher]

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Hyper-IgE Syndrome in an Infant.

J Cutan Med Surg. 2016 Jan 22;

Authors: Giberson M, Finlayson L

Abstract
BACKGROUND: Hyper-immunoglobulin E syndrome (HIES) is a rare primary immunodeficiency disorder that affects multiple systems. One of the early findings is a papulopustular rash, which has a wide differential diagnosis.
METHOD: The authors report the case of a male newborn diagnosed with HIES. He presented with papulopustular dermatitis on the scalp. The authors also present a review of current theory on the pathophysiology, clinical presentation, and management of HIES.
CONCLUSION: Although HIES is a multisystem disorder, many of the manifestations of HIES may present after the neonatal period. The cutaneous manifestations of HIES are usually present shortly after birth, and the presentation of pustules in a newborn may be one of the reasons a dermatologist would be asked to assess a patient in the neonatal period.

PMID: 26801049 [PubMed – as supplied by publisher]

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Primary immunodeficiencies worldwide: an updated overview from the Jeffrey Modell Centers Global Network.

Immunol Res. 2016 Jan 22;

Authors: Modell V, Quinn J, Orange J, Notarangelo LD, Modell F

Abstract
Primary immunodeficiencies (PI) are defects of the immune system that cause severe, sometimes life-threatening, infections if not diagnosed and treated appropriately. Many patients with PI are undiagnosed, under-diagnosed, or misdiagnosed. To raise awareness and assure earliest diagnosis, appropriate treatment, and proper care management, the Jeffrey Modell Foundation (JMF) implemented a physician education and public awareness program beginning in 2003. Data are requested annually from physician experts within the Jeffrey Modell Centers Network (JMCN), consisting of 602 expert physicians, at 253 academic institutions, in 206 cities, and 84 countries spanning six continents. Center Directors reported on patients’ specific PI defects and treatment modalities including immunoglobulins, transplantation, and gene therapy as well as data on gender and age. Center Directors also provided physician-reported patient outcomes as well as pre- and post-diagnosis differences. Costs were assigned to these factors. In collaboration with the Network, JMF advocated, funded, and implemented population-based newborn screening for severe combined immunodeficiency and T cell lymphopenia, covering 96.2 % of all newborns in the US. Finally, 21 JMF Centers participated in a polio surveillance study of patients with PI who either received or have been exposed to the oral polio vaccine. These initiatives have led to an overall better understanding of the immune system and will continue to improve quality of life for those with PI.

PMID: 26802037 [PubMed – as supplied by publisher]

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Sclerosing Cholangitis: Clinicopathologic Features, Imaging Spectrum, and Systemic Approach to Differential Diagnosis.

Korean J Radiol. 2016 Jan-Feb;17(1):25-38

Authors: Seo N, Kim SY, Lee SS, Byun JH, Kim JH, Kim HJ, Lee MG

Abstract
Sclerosing cholangitis is a spectrum of chronic progressive cholestatic liver disease characterized by inflammation, fibrosis, and stricture of the bile ducts, which can be classified as primary and secondary sclerosing cholangitis. Primary sclerosing cholangitis is a chronic progressive liver disease of unknown cause. On the other hand, secondary sclerosing cholangitis has identifiable causes that include immunoglobulin G4-related sclerosing disease, recurrent pyogenic cholangitis, ischemic cholangitis, acquired immunodeficiency syndrome-related cholangitis, and eosinophilic cholangitis. In this review, we suggest a systemic approach to the differential diagnosis of sclerosing cholangitis based on the clinical and laboratory findings, as well as the typical imaging features on computed tomography and magnetic resonance (MR) imaging with MR cholangiography. Familiarity with various etiologies of sclerosing cholangitis and awareness of their typical clinical and imaging findings are essential for an accurate diagnosis and appropriate management.

PMID: 26798213 [PubMed – in process]

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Role of apoptosis in common variable immunodeficiency and selective immunoglobulin A deficiency.

Mol Immunol. 2016 Jan 12;71:1-9

Authors: Yazdani R, Fatholahi M, Ganjalikhani-Hakemi M, Abolhassani H, Azizi G, Hamid KM, Rezaei N, Aghamohammadi A

Abstract
Common variable immunodeficiency (CVID) and selective IgA deficiency (SIgAD) are the most common primary immunodeficiencies in human. Both diseases share clinical manifestation and molecular defects. Increased apoptosis may be one of the mechanisms involved in the pathogenesis of CVID and SIgAD. Elevated apoptosis in this disorder leads to defective long-term survival of B-cells, reduced antibody production, decreased lymphocyte proliferation and defective cytokine secretion. For the first time, we reviewed the role of apoptosis in CVID and SIgAD.

PMID: 26795881 [PubMed – as supplied by publisher]

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