The plethora, clinical manifestations and treatment options of autoimmunity in patients with primary immunodeficiency

Abstract

Aim: Although the association between primary immunodeficiency and autoimmunity is already well-known, it has once again become a topic of debate with the discovery of newly-defined immunodeficiencies. Thus, investigation of the mechanisms of development of autoimmunity in primary immunodefficiency and new target-specific therapeutic options has come to the fore. In this study, we aimed to examine the clinical findings of autoimmunity, autoimmunity varieties, and treatment responses in patients who were genetically diagnosed as having primary immunodeficiency. Material and Methods:The files of patients with primary immunodeficiency who had clinical findings of autoimmunity, who were diagnosed genetically, and followed up in our clinic were investigated. The demographic and clinical features of the patients and their medical treatments were evaluated.Results: Findings of autoimmunity were found in 30 patients whose genetic mutations were identified. The mean age at the time of the first symptoms was 8.96±14.64 months, and the mean age of receiving a genetic diagnosis was 82.55±84.71 months. The most common diseases showing findings of autoimmunity included immune dysregulation, polyendocrinopathy, enteropathy X-linked syndrome (16.7%); autoimmune lymphoproliferative syndrome (10%); lipopolysaccharide-responsive beige-like anchor protein deficiency (10%); and DiGeorge syndrome (10%). Twelve (40%) patients showed findings of autoimmunity at the time of first presentation. The most common findings of autoimmunity included inflammatory bowel disease, inflammatory bowel disease-like findings (n=14, 46.7%), immune thrombocytopenic purpura (n=11, 36.7%), and autoimmune hemolytic anemia (n=9, 30.0%). A response to immunosupressive agents was observed in 15 (50%) patients. Ten patients underwent hematopoietic stem cell transplantation. Six patients were lost to follow-up due to a variety of complications. Conclusion:Autoimmunity is frequently observed in patients with primary immunodeficiency. The possibility of primary immunodeficiency should be considered in patients with early-onset manifestations of autoimmunity, and these patients should be carefully monitored in terms of immunodeficiency development. Early diagnosis of primary immunodeficiency may provide favorable outcomes in terms of survival. (Turk Pediatri Ars 2016; 51: 186-92)

The Changing Landscape of Autoimmune Hemolytic Anemia

“…Several case reports exist for AIHA association with systemic sclerosis, Sjögren syndrome (SS), autoimmune liver disorders, and inflammatory bowel diseases (7,11). Moreover, various immunodeficiencies have been identified as predisposing conditions for AIHA, including common variable immunedeficiency (19), IgA deficiency, and autoimmune lymphoproliferative syndromes (ALPS) (20). Interestingly, mutations in genes implicated in primary immunodeficiencies (TNFRSF6, CTLA4, STAT3, PIK3CD, CBL, ADAR1, LRBA, RAG1, and KRAS) have been detected in about half of pediatric patients with AIHA and ITP (Evans Syndrome, ES); mutated patients showed more severe disease with higher treatment requirement and fatal outcome (12).…”

Differential Behavior of Non-albicans Candida Species in the Central Nervous System of Immunocompetent and Immunosuppressed Mice

“…High doses of glucocorticoids induced apoptosis of T cells and other immune cells such as thymocytes, B cells, macrophages, mature dendritic cells, eosinophils, and natural killer cells (Gruver-Yates and Cidlowski, 2013), but did not affect monocytes and neutrophils (Serra-Bonett et al, 2009). Even though the literature concerning this subject is very scarce and also indirect, this possibility is supported by some findings as the presence of neutrophilic leukocytosis in children with nephrotic syndrome being treated with systemic corticosteroids (Bariş et al, 2016) and enhanced survival and function of neutrophils and alveolar macrophages by inhaled glucocorticoids (Schleimer, 2004). Interestingly, during systemic candidiasis there is an accumulation of neutrophils in all organs, except the brain (Lionakis et al, 2011) and these cells are able to produce a plethora of cytokines including, for example, TNF-α, IL-6, IL-10 and IL-5 (Tecchio et al, 2014; Xu et al, 2017) that were found elevated in spleen cell cultures from prednisolone treated mice, as described above.…”

APECED in Turkey: A case report and insights on genetic and phenotypic variability

“…In this manuscript we present the clinical, immunological and genetic features of a new case of APECED and review in the literature from 2000 to date a Turkish APECED series of patients, mostly diagnosed on clinical findings [29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45]. Results of the analysis were compared with those retrieved on Finnish, Sardinian and North/South American cohorts [9,10,28] based on classic versus novel Ferre/ (continued on next page)…”