Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Incomplete deletion of KRN T cells that recognize the ubiquitously expressed self-antigen glucose-6-phosphate-isomerase (GPI) initiates an anti-GPI autoimmune cascade in K/BxN mice resulting in a humorally mediated arthritis. Transgenic (Tg) expression of a KRN T cell receptor (TCR) agonist under the major histocompatibility complex class II promoter resulted in thymic deletion with loss of anti-GPI T and B cell responses and attenuated arthritis course. However, double Tg mice succumbed to systemic autoimmunity with multiorgan inflammation and autoantibody production. Extensive thymic deletion resulted in lymphopenia and elimination of CD4+ CD25+ regulatory T cells (Tregs), but spared some CD4+ T cells expressing endogenous TCR, which oligoclonally expanded in the periphery. Disease was transferred by these T cells and prevented by cotransfer of CD4+ CD25+ Tregs. Moreover, we extended our findings to another TCR system (anti-hen egg lysozyme [HEL] TCR/HEL mice) where similarly extensive thymic deletion also resulted in disease. Thus, our studies demonstrated that central tolerance can paradoxically result in systemic autoimmunity through differential susceptibility of Tregs and autoreactive T cells to thymic deletion. Therefore, too little or too much negative selection to a self-antigen can result in systemic autoimmunity and disease.
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PMID:Massive thymic deletion results in systemic autoimmunity through elimination of CD4+ CD25+ T regulatory cells. 1474 95

Mendelian disorders in glucose-6-phosphate metabolism can present with inflammatory bowel disease [IBD]. Using whole genome sequencing we identified a homozygous variant in the glucose-6-phosphatase G6PC3 gene [c.911dupC; p.Q305fs*82] in an adult patient with congenital neutropenia, lymphopenia and childhood-onset, therapy-refractory Crohn's disease. Because G6PC3 is expressed in several haematopoietic and non-haematopoietic cells it was unclear whether allogeneic stem cell transplantation [HSCT] would benefit this patient with intestinal inflammation. We show that HSCT resolves G6PC3-associated immunodeficiency and the Crohn's disease phenotype. It illustrates how even in adulthood, next-generation sequencing can have a significant impact on clinical practice and healthcare utilization in patients with immunodeficiency and monogenic IBD.
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PMID:Remission of Inflammatory Bowel Disease in Glucose-6-Phosphatase 3 Deficiency by Allogeneic Haematopoietic Stem Cell Transplantation. 3115 58