Infectious and non-infectious complications in primary immunodeficiency disorders: an autopsy study from North India

Gupta, Kirti; Rawat, Amit; Agrawal, Parimal; Jindal, Ankur Kumar; Nada, Ritambhra; Saikia, Biman; Chan, Koon Wing; Lau, Yu Lung; Minz, Ranjana Walker; Singh, Surjit

doi:10.1136/jclinpath-2017-204708

Cited by 8 publications

(3 citation statements)

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“…We also noted a high rate of disseminated CMV infection (8.3%) in our cohort. However, several amongst these were identified only on autopsy ( 60 ). This underscores the importance of vigilant screening and preventive measures for CMV infection in children with SCID.…”

Section: Discussionmentioning

confidence: 99%

Clinical, Immunological, and Molecular Features of Severe Combined Immune Deficiency: A Multi-Institutional Experience From India

Vignesh¹,

Rawat²,

Kumrah³

et al. 2021

Front. Immunol.

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BackgroundSevere Combined Immune Deficiency (SCID) is an inherited defect in lymphocyte development and function that results in life-threatening opportunistic infections in early infancy. Data on SCID from developing countries are scarce.ObjectiveTo describe clinical and laboratory features of SCID diagnosed at immunology centers across India.MethodsA detailed case proforma in an Excel format was prepared by one of the authors (PV) and was sent to centers in India that care for patients with primary immunodeficiency diseases. We collated clinical, laboratory, and molecular details of patients with clinical profile suggestive of SCID and their outcomes. Twelve (12) centers provided necessary details which were then compiled and analyzed. Diagnosis of SCID/combined immune deficiency (CID) was based on 2018 European Society for Immunodeficiencies working definition for SCID.ResultsWe obtained data on 277 children; 254 were categorized as SCID and 23 as CID. Male-female ratio was 196:81. Median (inter-quartile range) age of onset of clinical symptoms and diagnosis was 2.5 months (1, 5) and 5 months (3.5, 8), respectively. Molecular diagnosis was obtained in 162 patients - IL2RG (36), RAG1 (26), ADA (19), RAG2 (17), JAK3 (15), DCLRE1C (13), IL7RA (9), PNP (3), RFXAP (3), CIITA (2), RFXANK (2), NHEJ1 (2), CD3E (2), CD3D (2), RFX5 (2), ZAP70 (2), STK4 (1), CORO1A (1), STIM1 (1), PRKDC (1), AK2 (1), DOCK2 (1), and SP100 (1). Only 23 children (8.3%) received hematopoietic stem cell transplantation (HSCT). Of these, 11 are doing well post-HSCT. Mortality was recorded in 210 children (75.8%).ConclusionWe document an exponential rise in number of cases diagnosed to have SCID over the last 10 years, probably as a result of increasing awareness and improvement in diagnostic facilities at various centers in India. We suspect that these numbers are just the tip of the iceberg. Majority of patients with SCID in India are probably not being recognized and diagnosed at present. Newborn screening for SCID is the need of the hour. Easy access to pediatric HSCT services would ensure that these patients are offered HSCT at an early age.

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Section: Discussionmentioning

confidence: 99%

Clinical, Immunological, and Molecular Features of Severe Combined Immune Deficiency: A Multi-Institutional Experience From India

Vignesh¹,

Rawat²,

Kumrah³

et al. 2021

Front. Immunol.

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“…Similarly, several primary immunodeficiencies have been associated with AA amyloidosis, including common variable immunodeficiency, 121‐130 X‐linked agammaglobulinemia, 131‐134 cyclic neutropenia, 135 chronic granulomatous disease, 84,136,137 hyperimmunoglobulin E syndrome, 138 and leucocyte adhesion deficiency 139 …”

Section: Infections Associated With Aa Amyloidosismentioning

confidence: 99%

Infections and AA amyloidosis: An overview

et al. 2021

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Background Amyloidoses are a heterogeneous group of systemic diseases characterised by extracellular accumulation of insoluble amyloid fibrils derived from unfolded proteins. Inflammatory (AA) amyloidosis can complicate various inflammatory disorders that are associated with a sustained acute phase response and serum amyloid A (SAA) protein overproduction. Chronic infections were the first recognised cause of amyloidoses. However, with the better management of underlying diseases, the frequency of AA amyloidosis is decreasing. Purpose The aim of this overview was to discuss the several infections associated with AA amyloidosis and the relative frequency of infections as aetiological factors. Methods A search of the literature was performed using the PubMed database using the MeSH terms “Amyloidosis” and “Infections,” from inception to December 31st, 2019. Articles written in other languages than English or French were excluded. Results The frequency of AA amyloidosis secondary to infections decreased from more than 50% to less than 20% after the 2000s, with a parallel increase in the frequency of AA amyloidosis secondary to inflammatory diseases and to an unknown cause. Conclusion Whereas new antibiotics have been developed and sanitary conditions are better, infections still represent 5%‐30% of the causes of AA amyloidosis, including in developed countries. These data argue for better screening of chronic infections to prevent AA amyloidosis and the development of new strategies to manage recurrent infections.

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“…no signs of concomitant HIV infection or genetic causes of severe immunodeficiency), the immune systems of neonates and infants are immature with suboptimal responses to infections and vaccines . Viral adrenalitis in primary immunodeficiencies have also been described, including adrenal insufficiency caused by Epstein–Barr virus (EBV) infection in an adolescent with Wiscott–Aldrich syndrome and subclinical adrenal CMV infection discovered at autopsy in children with severe combined immunodeficiency . However, some of the viruses described above, including HSV‐1 and CMV, have also been associated with adrenalitis in apparently immunocompetent adults .…”

Section: Microbial Causes Of Adrenal Insufficiencymentioning

confidence: 99%

The potential role for infections in the pathogenesis of autoimmune Addison’s disease

Hellesen

Bratland

2018

Clinical and Experimental Immunology

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Autoimmune Addison's disease (AAD), or primary adrenocortical insufficiency, is a classical organ-specific autoimmune disease with 160 years of history. AAD is remarkably homogeneous with one major dominant self-antigen, the cytochrome P450 21-hydroxylase enzyme, which is targeted by both autoantibodies and autoreactive T cells. Like most autoimmune diseases, AAD is thought to be caused by an unfortunate combination of genetic and environmental factors. While the number of genetic associations with AAD is increasing, almost nothing is known about environmental factors. A major environmental factor commonly proposed for autoimmune diseases, based partly on experimental and clinical data and partly on shared pathways between anti-viral immunity and autoimmunity, is viral infections. However, there are few reports associating viral infections to AAD, and it has proved difficult to establish which immunological processes that could link any viral infection with the initiation or progression of AAD. In this review, we will summarize the current knowledge on the underlying mechanisms of AAD and take a closer look on the potential involvement of viruses.

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Infectious and non-infectious complications in primary immunodeficiency disorders: an autopsy study from North India

Abstract: The present study is perhaps the first autopsy series on PID. Even in the molecular era, such analysis is still important, as correlation of pathological features with clinical symptoms provides clues for a timely diagnosis and appropriate therapeutic intervention.

Cited by 8 publications

References 37 publications

Clinical, Immunological, and Molecular Features of Severe Combined Immune Deficiency: A Multi-Institutional Experience From India

Clinical, Immunological, and Molecular Features of Severe Combined Immune Deficiency: A Multi-Institutional Experience From India

Infections and AA amyloidosis: An overview

The potential role for infections in the pathogenesis of autoimmune Addison’s disease

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