Research

Vaccine-Derived Polioviruses and Children with Primary Immunodeficiency, Iran, 1995-2014.

Emerg Infect Dis. 2016 Oct;22(10):1712-1719

Authors: Shaghaghi M, Shahmahmoodi S, Abolhassani H, Soleyman-Jahi S, Parvaneh L, Mahmoudi S, Chavoshzadeh Z, Yazdani R, Zahraei SM, Ebrahimi M, Eslamian MH, Tabatabaie H, Yousefi M, Kandelousi YM, Oujaghlou A, Rezaei N, Aghamohammadi A

Abstract
Widespread use of oral poliovirus vaccine has led to an ≈99.9% decrease in global incidence of poliomyelitis (from ≈350,000 cases in 1988 to 74 cases in 2015) and eradication of wild-type poliovirus serotypes 2 and 3. However, patients with primary immunodeficiency might shed vaccine-derived polioviruses (VDPVs) for an extended period, which could pose a major threat to polio eradication programs. Since 1995, sixteen VDPV populations have been isolated from 14 patients with immunodeficiency in Iran. For these patients, vaccine-associated paralysis, mostly in >1 extremity, was the first manifestation of primary immunodeficiency. Seven patients with humoral immunodeficiency cleared VDPV infection more frequently than did 6 patients with combined immunodeficiencies. Our results raise questions about manifestations of VDPVs in immunodeficient patients and the role of cellular immunity against enterovirus infections. On the basis of an association between VDPVs and immunodeficiency, we advocate screening of patients with primary immunodeficiency for shedding of polioviruses.

PMID: 27648512 [PubMed – as supplied by publisher]

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Dual T cell- and B cell-intrinsic deficiency in humans with biallelic RLTPR mutations.

J Exp Med. 2016 Sep 19;

Authors: Wang Y, Ma CS, Ling Y, Bousfiha A, Camcioglu Y, Jacquot S, Payne K, Crestani E, Roncagalli R, Belkadi A, Kerner G, Lorenzo L, Deswarte C, Chrabieh M, Patin E, Vincent QB, Müller-Fleckenstein I, Fleckenstein B, Ailal F, Quintana-Murci L, Fraitag S, Alyanakian MA, Leruez-Ville M, Picard C, Puel A, Bustamante J, Boisson-Dupuis S, Malissen M, Malissen B, Abel L, Hovnanian A, Notarangelo LD, Jouanguy E, Tangye SG, Béziat V, Casanova JL

Abstract
Combined immunodeficiency (CID) refers to inborn errors of human T cells that also affect B cells because of the T cell deficit or an additional B cell-intrinsic deficit. In this study, we report six patients from three unrelated families with biallelic loss-of-function mutations in RLTPR, the mouse orthologue of which is essential for CD28 signaling. The patients have cutaneous and pulmonary allergy, as well as a variety of bacterial and fungal infectious diseases, including invasive tuberculosis and mucocutaneous candidiasis. Proportions of circulating regulatory T cells and memory CD4(+) T cells are reduced. Their CD4(+) T cells do not respond to CD28 stimulation. Their CD4(+) T cells exhibit a “Th2” cell bias ex vivo and when cultured in vitro, contrasting with the paucity of “Th1,” “Th17,” and T follicular helper cells. The patients also display few memory B cells and poor antibody responses. This B cell phenotype does not result solely from the T cell deficiency, as the patients’ B cells fail to activate NF-κB upon B cell receptor (BCR) stimulation. Human RLTPR deficiency is a CID affecting at least the CD28-responsive pathway in T cells and the BCR-responsive pathway in B cells.

PMID: 27647349 [PubMed – as supplied by publisher]

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Autoinflammatory diseases: update on classification diagnosis and management.

J Clin Pathol. 2016 Sep 19;

Authors: Pathak S, McDermott MF, Savic S

Abstract
The spectrum of systemic autoinflammatory disorders broadens continually. In part, this is due to the more widespread application of massive parallel sequencing, helping with novel gene discovery in this and other areas of rare diseases. Some of the conditions that have been described fit neatly into a conventional idea of autoinflammation. Others, such as interferon-mediated autoinflammatory diseases, are broadening the concept which we consider to be autoinflammatory disorders. There is also a widening of the clinical phenotypes associated with certain genetic mutations, as genetic testing is used more regularly and increasing numbers of patients are screened. It is also increasingly evident that both autoinflammatory and autoimmune problems are frequently seen as complications of primary immunodeficiency disorders. The aim of this review is to provide an update on some recently discovered conditions and to discuss how these disorders help to define the concept of autoinflammation. The review will also cover recent discoveries in the biology of innate-immune-mediated inflammation and describe how this has provided the biological rationale for using anti-interleukin-1 therapies in the treatment of many such conditions. Finally, we discuss the importance of recognising somatic mutations as causes of autoinflammatory clinical phenotypes and provide practical advice on how this could be tackled in everyday clinical practice.

PMID: 27646526 [PubMed – as supplied by publisher]

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Association of interleukin-6 single nucleotide polymorphisms with juvenile idiopathic arthritis.

Clin Rheumatol. 2016 Sep 20;

Authors: Ziaee V, Maddah M, Moradinejad MH, Rezaei A, Zoghi S, Sadr M, Harsini S, Rezaei N

Abstract
Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children. Genetics and inflammatory elements seem to act as major underlying factors in its pathogenesis. The aim of this study is to identify the associations between interleukin-6 (IL-6) gene polymorphisms and individuals’ vulnerability to JIA in a group of Iranian pediatric patients. Fifty-four patients with JIA were enrolled in this investigation and compared with 139 healthy individuals. Using polymerase chain reaction with sequence-specific primers, cytokine genotyping was performed. The allele and genotype frequencies of two single nucleotide polymorphisms (SNPs) within the IL-6 gene at -174 and +565 positions were assessed. A significant positive association was observed for IL -6 -174 G allele in the patient group (p = 0.02). Furthermore, a positive association was observed in patients with JIA for the GG genotype at the same position (p < 0.01), thus revealing a predisposing effect in JIA patients. On the other hand, a significant negative association was found for IL-6 -174 CG genotype (p < 0.01) in the case group. No significant difference was discovered in both the allelic and genotypic frequencies of IL-6 +565 position between patients and controls. Additionally, haplotype analysis divulged over representation of IL-6 GG haplotype in patient group (p < 0.01) as well as IL-6 CG haplotype in healthy controls (p < 0.01). Certain allele, genotype, and haplotype in IL-6 gene were over expressed in patients with JIA, which probably could render individuals more susceptible to this disease.

PMID: 27646136 [PubMed – as supplied by publisher]

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[Liver abscess].

Rev Med Interne. 2016 Sep 14;

Authors: Rossi G, Lafont E, Gasperini L, Dokmak S, Ronot M, Rossi B, Zarrouk V, Fantin B, Lefort A

Abstract
Liver abscess is a rare and severe infection. Incidence increases because of aging of population, advances in liver and biliary surgery including liver transplantation, and immunodeficiency factors. Diagnosis depends mainly on imaging and needle aspiration for microbiological identification. Treatment is based on antibiotics, percutaneous or surgical drainage, and control of the primary source.

PMID: 27639909 [PubMed – as supplied by publisher]

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Autoimmunity in common variable immunodeficiency: epidemiology, pathophysiology and management.

Expert Rev Clin Immunol. 2016 Sep 16;:1-15

Authors: Azizi G, Abolhassani H, Asgardoon MH, Alinia T, Yazdani R, Mohammadi J, Rezaei N, Ochs HD, Aghamohammadi A

Abstract
INTRODUCTION: Common variable immunodeficiency (CVID) comprises a large heterogeneous group of patients with primary antibody deficiency.
AREAS COVERED: The affected patients are characterized by increased susceptibility to infections and low levels of serum immunoglobulin. However, enteropathy, granulomatous organ infiltrates, malignancy, inflammatory and autoimmune conditions are also prevalent. The concomitance of immunodeficiency and autoimmunity appears to be paradoxical and creates difficulties in the management of autoimmune complications affecting these patients. Expert commentary: The management of autoimmunity in patients with CVID requires special considerations because dysregulation and dysfunctions of the immune system along with persistent inflammation impair the process of diagnosis and treatment.

PMID: 27636680 [PubMed – as supplied by publisher]

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The immunophenotypical fingerprint of patients with primary antibody deficiencies is partially present in their asymptomatic first-degree relatives.

Haematologica. 2016 Sep 15;

Authors: Bogaert DJ, De Bruyne M, Debacker V, Depuydt P, De Preter K, Bonroy C, Philippe’ J, Bordon V, Lambrecht BN, Kerre T, Cerutti A, Vermaelen KY, Haerynck F, Dullaers M

Abstract
The etiology of primary antibody deficiencies is largely unknown. Beside rare monogenic forms, the majority of cases seem to have a more complex genetic basis. Whereas common variable immunodeficiency has been investigated in-depth, only few reports exist on milder primary antibody deficiencies like idiopathic primary hypogammaglobulinemia and IgG subclass deficiency. We performed flow cytometric immunophenotyping in 33 common variable immunodeficiency, 23 idiopathic primary hypogammaglobulinemia and 21 IgG subclass deficiency patients, and in 47 asymptomatic first-degree family members of patients and 101 unrelated healthy controls. All three patient groups showed decreased memory B and naive T cell subsets and decreased B-cell activating factor receptor expression. In contrast, circulating follicular helper T cell frequency and expression of inducible T-cell co-stimulator and chemokine receptors were significantly altered in common variable immunodeficiency patients only. Asymptomatic first-degree family members of patients demonstrated similar, albeit intermediate, alterations in naive and memory B and T cell subsets. About 13% of asymptomatic relatives had an abnormal peripheral B cell composition. Furthermore, asymptomatic relatives showed decreased CD4+ recent thymic emigrants and increased central memory T cells. Serum IgG and IgM levels were also significantly lower in asymptomatic relatives compared to healthy controls. We conclude that, in our cohort, the immunophenotypical landscape in primary antibody deficiencies comprises a spectrum, in which some alterations are shared between all primary antibody deficiencies whereas others are only associated with common variable immunodeficiency. Importantly, asymptomatic first-degree family members of patients are found to have an intermediate phenotype for peripheral B and T cell subsets.

PMID: 27634199 [PubMed – as supplied by publisher]

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Chronic Giardiasis in a Case of Common Variable Immunodeficiency (CVID): A Case Report.

J Clin Diagn Res. 2016 Jul;10(7):DD03-DD04

Authors: Paranjpe SM, Koticha A, Mehta PR

Abstract
Common Variable Immunodeficiency (CVID) is a primary immunodeficiency characterized by low antibody levels and recurrent infections. This makes an individual more prone to recurrent respiratory and gastrointestinal tract infections. In cases where there is persistent positive finding of intestinal parasites in stool, a high index of suspicion should be raised to rule out immunodeficiency state. Early diagnosis of such cases will help in reducing the morbidity and better management of the patient. A case of CVID in 18-year-old male with recurrent lower respiratory tract infection and chronic diarrhoea due to Giardia lamblia is reported herewith.

PMID: 27630845 [PubMed – as supplied by publisher]

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A case report of primary orbital non-Hodgkin’s lymphoma causing complete vision loss.

GMS Ophthalmol Cases. 2016;6:Doc06

Authors: Lamba N, Dworak DP, Patel SA, Chennuri R

Abstract
A 29-year-old male with acquired immunodeficiency syndrome presented with a week of left eye blurriness, which then progressed to complete vision loss. On exam, the left pupil was nonreactive to light, and fundoscopy showed significant optic nerve edema. CT and MRI of the left orbit showed a mass lesion compressing the posterior aspect of the sclera with diffuse thickening and contrast enhancement of the retrobulbar portion of the left optic nerve. The lesion demonstrated low T1 and intermediate T2 intensities and heterogeneous contrast enhancement and measured 17.4 mm x 15 mm x 10.6 mm. Anterior orbitotomy with exploration and biopsy were performed. Immunohistochemical studies confirmed diffuse large B-cell lymphoma and a workup showed no systemic involvement. Plans for treatment with chemotherapy and radiation were initiated. Even though rare, primary orbital NHL should be in the differential for relatively acute blindness without other symptoms, especially in patients with AIDS.

PMID: 27625965 [PubMed]

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Successful immune reconstitution by means of hematopoietic stem cell transplantation in a Colombian patient with chronic granulomatous disease.

Biomedica. 2016;36(2):204-212

Authors: Rocha YC, López JÁ, Orrego JC, Coll Y, Karduss A, Rosenzweig S, Franco JL

Abstract
INTRODUCTION: Chronic granulomatous disease is a primary immunodeficiency that results from mutations in proteins of the NADPH oxidase system that affect the microbicidal activity of phagocytes. Immune reconstitution by hematopoietic stem cell transplantation is currently the only curative therapy for this disease. Objective: To describe the clinical and molecular characterization of a patient with X-linked chronic granulomatous disease and the successful immune reconstitution by means of a hematopoietic stem cell transplantation. Methods: The respiratory burst was measured by flow cytometry using the dihydrorodamine 123 (DHR) oxidation test in neutrophils of peripheral blood. Mutational analysis of CYBB was performed by PCR amplification in complementary DNA, as well as sequencing and comparative genomic hybridization in genomic DNA. HLA-identical stem cells from the patient’s younger brother were used for the transplantation and reduced intensity pre-transplantation conditioning was administered. Post-transplantation immune reconstitution was evaluated periodically by serial complete blood counts and DHR 123 in peripheral blood neutrophils. Results: The diagnosis of X-linked chronic granulomatous disease resulted from a hemizygous deletion affecting Xp21.1 that included the entire CYBB. Post-transplantation engraftment was documented in platelets and peripheral blood neutrophils at days 10 and 11, respectively. Total hematological reconstitution was achieved by day 30 post-transplantation and no complications or infections have been observed in the three years since the transplantation. Conclusion: Hemopoietic stem cell transplantation allows for total reconstitution of the immune function related to microbicidal activity of phagocytic cells from patients with X-linked chronic granulomatous disease.

PMID: 27622481 [PubMed – as supplied by publisher]

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