Manish Butte

Autoimmunity and immunodeficiency.

Curr Opin Rheumatol. 2020 Jan 20;:

Authors: Hoyos-Bachiloglu R, Chou J

Abstract
PURPOSE OF REVIEW: Advances in genomics and animal models of human disease have enabled the discovery of mechanisms important for host immunity and self-tolerance. Here, we summarize conceptual and clinical discoveries identified from 2018 to 2019 in the field of primary immunodeficiencies and autoimmunity.
RECENT FINDINGS: Three new primary immunodeficiencies with autoimmunity were identified and the clinical phenotypes of NFKB1 haploinsufficiency and RASGRP1 deficiency were expanded. A diversity of novel mechanisms leading to autoimmunity associated with primary immunodeficiencies (PIDs) was reported, including pathways important for the metabolism and function of regulatory T cells and germinal B cells, the contribution of neutrophil extracellular traps to plasmacytoid dendritic cell activation and the influence of commensal bacteria on the generation of autoantibodies. With regard to therapeutic developments in the field, we highlight the use of janus kinase inhibitors for immune dysregulation associated with gain-of-function variants in STAT1 and STAT3, as well as the risks of persistent hypogammaglobulinemia associated with rituximab treatment.
SUMMARY: Mechanistic studies of PIDs with autoimmunity elucidate key principles governing the balance between immune surveillance and self-tolerance.

PMID: 31977526 [PubMed – as supplied by publisher]

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Common Variable Immunodeficiency: A Standardized Patient Case for Second-Year Medical Students.

MedEdPORTAL. 2019 Oct 18;15:10837

Authors: Barilla-LaBarca ML, Rodriguez M, Connors K, Wanamaker T, Petrizzo MC

Abstract
Introduction: Common variable immunodeficiency (CVID) is the most common symptomatic antibody deficiency, with a prevalence of 0.6-6.9 depending on the population studied. In contrast to other primary immunodeficiency diseases (PIDDs), symptoms may not appear until the third decade of life. Lack of recognition of CVID is a persistent problem. Myriad confounding clinical phenotypes and frequent infections, including autoimmunity, malignancy, chronic lung disease, granulomatous disease, and gastrointestinal disease, complicate the diagnosis. Often it is years before a diagnosis is made, leading to irreversible morbidities and mortality.
Methods: Second-year medical students are introduced to CVID during their session on PIDDs that occurs during the immunology/rheumatology course. To assess students’ recognition of CVID, a 15-minute OSCE encounter was created that included a simulation of lung sounds (rhonchi), physical exam cards (clubbing, otitis media with effusion), and moulage of skin (petechiae). A standardized patient (SP) portrayed a patient requesting antibiotics for a sinus infection. Students were tasked to both interview the patient and perform a hypothesis-driven physical exam. A postencounter exercise queried the students on their differential diagnosis and their rationale.
Results: Item analysis of the case showed high levels of difficulty and strong discrimination between high- and low-performing students in both communication skills and clinical reasoning in CVID.
Discussion: This SP encounter can be used in both formative and summative assessments to measure the recognition of CVID.

PMID: 31976361 [PubMed – in process]

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[Ichtyosiform erythroderma revealing a severe combined immunodeficiency].

Ann Dermatol Venereol. 2020 Jan 20;:

Authors: Ghariani Fetoui N, Boussofara L, Hmida D, Mokni S, Mekki N, Ben Mustapha I, Belajouza C, Ghariani N, Picard C, Denguezli M

Abstract
BACKGROUND: Severe combined immunodeficiency (SCID) is a the most severe form of primary immunodeficiency and is highly heterogeneous. We report an atypical form of SCID revealed by exfoliative erythroderma.
PATIENTS AND METHODS: A 3-month-old boy, born to consanguineous parents, was admitted to the dermatology department with exfoliative erythroderma associated with eczematous patches and alopecia of the scalp, eyelashes, and eyebrows, but with no lymphadenopathy or hepatosplenomegaly. He displayed chronic diarrhea and recurrent infection since birth. A complete blood count showed marked leukocytosis with eosinophilia and lymphocytosis. These clinical and biological findings improved partly with topical steroids. The patient no longer had erythroderma and showed regrowth of hair, eyelashes and eyebrows. The subsequent CBC showed less marked eosinophilia with mild lymphopenia and no leukocytosis. Immunoglobulin levels were undetectable. Primary immunodeficiency was discussed. Immunological investigations concluded on a diagnosis of T-B-NK+ SCID. Mutation analysis revealed a homozygous c.1338C>G (pCys446Trp) mutation in the RAG2 gene. Hematopoietic stem cell transplantation is planned in the near future.
CONCLUSION: This case illustrates atypical T-B-NK+ SCID revealed by severe exfoliative erythroderma in a 3-month-old boy with RAG2 gene mutation. Neonatal erythroderma must be considered a warning sign of primary immunodeficiency requiring immediate immunological phenotyping as well as genetic testing for a definitive diagnosis.

PMID: 31973905 [PubMed – as supplied by publisher]

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X-Linked Hyper IgM Syndrome Presenting with Recurrent Tuberculosis-a Case Report.

J Clin Immunol. 2020 Jan 22;:

Authors: Krishnan VP, Taur P, Pandrowala A, Madkaikar M, Desai M

Abstract
The hyper IgM syndromes are a group of rare primary immunodeficiency disorders. Currently 6 classes of HIGM are described. X-linked HIGM is also called the type 1 HIGM is the commonest variant in which children present in early infancy with features of combined immunodeficiency. Tuberculosis is a very rare presentation as a presenting symptom in HIGM. Here, we describe a child with XHIGM with recurrent tuberculosis.

PMID: 31970544 [PubMed – as supplied by publisher]

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Comprehensive clinical and immunological features of 62 adult patients with selective primary IgM deficiency.

Am J Clin Exp Immunol. 2019;8(6):55-67

Authors: Lucuab-Fegurgur DL, Gupta S

Abstract
Selective IgM Deficiency (SIgMD) is a recently incorporated disorder in the classification of primary immunodeficiency diseases. The purpose of this study was to present detailed clinical and immunological features in a cohort of 62 adult patients with SIgMD. A retrospective chart review of 62 patients between 2009 and 2017 with a diagnosis of SIgMD was performed for clinical and immunological features, and response to immunoglobulin therapy in symptomatic patients who also exhibited specific antibody deficiency. The majority of patients presented with recurrent and chronic upper and lower respiratory tract infections (73%), most often with recurrent sinusitis (29%), bronchitis (33%), pneumonia (21%), and recurrent urinary tract infections (16%). Forty three percent of patients had associated autoimmune diseases including Hashimoto’s thyroiditis, and systemic lupus erythematosus. Approximately 35% of patients had atopic diseases, including allergic rhinitis and asthma. CD3+ T, CD4+ T, CD8+ T, and CD19+ B cells were normal in the majority of patients. IgG subclass deficiency was observed in approximately 22% of cases. Forty seven percent of patients exhibited specific anti-pneumococcal antibody deficiency. The six most common pneumococcal serotypes that were impaired in majority (>70%) of subjects included 3, 4, 9V, 9N, 12F, 23F. Eighteen (66%) of 27 patients with specific antibody deficiency received immunoglobulin therapy and almost all subjects responded to immunoglobulin therapy by decreased frequency of infections. No correlation was observed in immunological features, clinical manifestations, or response to therapy with serum IgM levels.

PMID: 31970029 [PubMed]

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Etiologic spectrum of interstitial lung diseases in Chinese children older than 2 years of age.

Orphanet J Rare Dis. 2020 Jan 22;15(1):25

Authors: Tang X, Li H, Liu H, Xu H, Yang H, Liu J, Zhao S

Abstract
BACKGROUND: Childhood interstitial lung diseases (ILD) (chILD) refer to a rare heterogeneous group of disorders. Global collaborations have been working on the etiologies and classification scheme of chILD. With the development of medical technologies, some new diseases were identified to be associated with chILD and its etiologic spectrum is expanding. The aim of this study is to describe the etiologic spectrum of chILD in children older than 2 years of age and summarize the approaches to diagnosis of chILD.
METHODS: We made a retrospective analysis of children older than 2 years of age with chILD who referred to Beijing Children’s Hospital from 21 provinces all over China from 2013 to 2018. After excluding pulmonary infection, congenital heart disease, bronchopulmonary dysplasia, bronchiolitis obliterans and bronchiectasis, 133 patients were included and categorized by etiology. Clinical manifestations, high-resolution computed tomography, laboratory data, genetic data and pathologic findings were all collected and reviewed.
RESULTS: Systemic disease associated ILD were the most common causes, accounting for 49.6% of the patients, followed by alveolar structure disorder-associated ILD (27%), exposure related ILD (13.5%), and disorders masquerading as ILD (3.8%). In systemic disease associated ILD, in addition to common etiologies such as vasculitis (10.5%) and connective tissue diseases (9.0%), primary immunodeficiency diseases (PID) associated ILD (9.8%), interstitial pneumonia with autoimmune features (6.8%), and metabolic diseases (6.8%) were not rarely found. Some newly reported etiologies such as STING-associated vasculopathy with onset in infancy, COPA syndrome and STAT3 mutation were included in PID associated ILD. Genetic tests contributed to 15% of the diagnoses which mainly distributed in PID associated ILD, metabolic diseases and surfactant dysfunction disorders, and contributed to the final diagnoses more than lung biopsies (13.5%) and biopsies of rashes or other tissues (12%).
CONCLUSIONS: This study first demonstrated an etiologic spectrum of chILD in Chinese children older than 2 years of age and summarized the approaches to diagnosis. The etiologic spectrum of chILD is expanding with more genetic etiologies being recognized.

PMID: 31969166 [PubMed – in process]

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