Immunodeficiency and rheumatic diseases musculoskeletal key brain anoxia

Early diagnosis has a significant impact on the prognosis of pids and has lifesaving implications. Timely treatment prevents organ damage and improves chance of cure by hematopoietic stem cell transplant in diseases amenable to such treatments. While definitive diagnosis of pids may require sophisticated functional and molecular studies, a significant proportion of pids can be picked up by simple tests such as full blood count and serum immunoglobulin levels. Absolute lymphocyte count (ALC) should be interpreted according to age-matched reference range. The fact that ALC 2.5 × 10 9/L is abnormal in infants is often under-recognized.

Lymphopenia is common in some rheumatological disorders such as systemic lupus erythematosus (SLE) especially after commencement of immunosuppressive treatment, but if accompanied by recurrent or unusual infections and autoimmunity, lymphocyte subset should be performed to exclude T-cell immunodeficiency.Brain anoxia genetic defects in cytokine and T-cell receptor signaling, V(D)J recombination, and basic cellular processes such as purine and pyrimidine metabolism classically cause severe combined immunodeficiencies (SCID) which usually present in infancy with limited survival. However, it is increasingly recognized that patients with “leaky” SCID can present later in life with recurrent infections and autoimmune manifestations [ 11].

Advances in the diagnosis and management of PID have taken place in india during the past 10–15 years. According to a recent review by sudhir gupta et al. [ 17], a total of 820 cases were evaluated for suspected PID from 2007 to 2010 in the institute of immunohaematology, mumbai.Brain anoxia of these 820 cases, 122 cases were diagnosed with PID. In the postgraduate institute of medical education and research, chandigarh, a total of 153 cases were diagnosed with PID from 1992 to 2010. Majority of the PID patients in chandigarh (41.9 %) had predominantly antibody deficiency diseases, which included XLA, X-HIM, AR-HIM, common variable immunodeficiency (CVID), selective iga deficiency with or without igg2 subclass deficiency, isolated igg2 subclass deficiency, and prolonged transient hypogammaglobulinemia. In mumbai, 15.5 % of patients were reported to have predominantly antibody deficiency diseases. Interestingly, around 30 % of PID patients in mumbai had diseases of immune dysregulation, including perforin deficiency, munc 13–4/syntax 11 deficiency, griscelli syndrome II, chédiak-higashi syndrome, hermansky-pudlak syndrome II, and autoimmune lymphoproliferative syndrome (ALPS) [ 18].Brain anoxia only one patient with autoinflammatory disorder (TRAPS-TNFR-associated periodic fever) was reported in chandigarh, but none from mumbai. The incidence of various pids in the two centers differs significantly. This may reflect differences in patterns and number of referrals to each center, as well as diagnostic tools and expertise available at each of these institutions. Furthermore, a possibility of racial and ethnic differences cannot be excluded. It is possible that different pids may be clustered in these regions, for example, WAS in northern india (chandigarh) and immunodeficiency with hypopigmentation in western india (mumbai).

The thymic epithelial cells express tissue-specific antigens needed for negative selection under the influence of autoimmune regulator ( AIRE) gene.Brain anoxia developing thymocytes with a T-cell receptor that recognizes these self-antigens undergo apoptosis during development, the so-called negative selection, to generate central immune tolerance. Genetic defects in the AIRE gene result in autoimmune polyendocrinopathy, candidiasis, and ectodermal dysplasia (APECED) syndrome, caused by failure of deletion of autoreactive T-cells [ 20]. Typical clinical presentations include mucocutaneous candidiasis (75 % by 5 years of age), autoimmune hypoparathyroidism (89 % by 10 years of age), and adrenocortical failure (60 % by 15 years of age). Susceptibility to candidiasis is related to autoantibodies against type I interferons and th17 cytokines which mediate antifungal immunity.Brain anoxia other autoimmune manifestations include thyroiditis, hepatitis, primary biliary cirrhosis, hypogonadism, autoimmune hemolytic anemia (AIHA), pernicious anemia, type 1 diabetes mellitus (DM), keratoconjunctivitis, vitiligo, alopecia, and ectodermal dysplasia [ 21].

Naturally occurring treg cells produced during the normal process of maturation in the thymus are potent immune suppressor cells. Disruption of the development and function of treg cells is a primary cause of autoimmune and inflammatory diseases [ 23]. Treg cells express CD4+, CD25+, and forkhead box P3 (foxp3). FoxP3 is a transcription factor which is required for the development and function of treg. Mutations in FOXP3 result in a disease entity called immunodysregulation, polyendocrinopathy, and enteropathy X-linked (IPEX) syndrome, which usually presents with the clinical triad of enteropathy, endocrinopathy (type I DM or thyroid disease), and eczema within the first few months of life.Brain anoxia other autoimmune manifestations include autoimmune cytopenia, membranous nephropathy, hepatitis, adrenal failure, pemphigoid nodularis, psoriasiform dermatitis, vasculitis, vitiligo, and alopecia. In most cases, IPEX is a fatal disease and causes death before the age of two. Patients with milder disease-associated hypomorphic mutations may be diagnosed in adolescence or even adulthood [ 24].

Autoantibody production may occur in B-cell intrinsic defects or in disorders with disturbed interaction between T-cells and B-cells. When B-cell maturation is impaired, central and peripheral checkpoints of B-cell receptor generation become dysfunctional, leading to impaired induction of B-cell tolerance as autoreactive clones are not eliminated.Brain anoxia this results in an apparent paradox of hypogammaglobulinemia and autoantibody production [ 26]. Autoimmunity is frequently observed in CVID. Approximately 25 % of patients with CVID have autoimmune manifestations. Common autoimmune manifestations include AIHA, ITP, pernicious anemia, thyroiditis, inflammatory bowel disease or villous atrophy, hepatitis, primary biliary cirrhosis, and alopecia. The incidence of rheumatological conditions such as rheumatoid arthritis, juvenile idiopathic arthritis, SLE, dermatomyositis, and vitiligo is already increased. Lymphoproliferative diseases are also seen, including interstitial pneumonia, sarcoid-like granuloma, and lymphoma [ 27]. Mechanisms leading to autoimmunity are related to B-cell abnormalities in peripheral tolerance, signaling, and maturation, as well as loss of treg cells [ 28].Brain anoxia

Genetic defects leading to complete abrogation of T-cell development and differentiation result in profound deficiency in peripheral T-cells [ 29]. However, in partial T-cell immunodeficiency disorders, T-cells are present but in reduced numbers or with reduced functions. Immune tolerance evolves in the context of a complete peripheral T-cell niche. Under conditions of partial thymic immunodeficiency, a reduced number of successful thymocytes mature and enter the peripheral circulation. This results in oligoclonal expansion and “holes” in the T-cell receptor repertoire for both tregs and autoreactive T-cells. A limited regulatory T-cell repertoire favors clonal expansion of autoreactive T-cell repertoire and hence disturbs the tolerogenic balance [ 30].Brain anoxia therefore, partial T-cell deficiency disorders are not only associated with impaired immune defense but also frequently exhibit immune dysregulation because of effector T-cell hyperactivity. Patients with “leaky” SCID caused by hypomorphic mutations may present in childhood with autoimmunity in addition to susceptibility to infections. Autoimmune manifestations are common in 22q11 microdeletion syndrome and include cytopenia, autoimmune hemolytic anemia (AIHA), thyroiditis, inflammatory bowel disease, arthritis, psoriasis, and vitiligo [ 31].