Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the relationship between CD5+ B cells and the activity of the disease process in patients with autoimmune diseases. In rheumatoid arthritis (RA), levels of CD5+ B cells were associated with autoantibody production as determined by serum rheumatoid factor and antinuclear antibodies. In addition, CD5+ B cells were significantly correlated with C-reactive protein, and data from longitudinal studies showed a marked influence of corticosteroid treatment on numbers of CD5+ B cells. Patients with systemic lupus erythematosus (SLE) had slightly elevated levels of CD5+ B cells as compared with normals, but a close association with measures of an active disease was not observed. In a group of patients with type I diabetes mellitus, CD5+ B cells were detected in patients with anti-islet cell antibodies. Our results suggest that CD5+ B cells are related to the activity of the autoimmune process and can be modulated by therapy in patients with RA. Although CD5+ B cells do not seem to have a major role in SLE, polyclonal activation might affect this B cell subset as well in this disease. Further studies are needed to define the precise role of CD5+ B cells in organ-specific autoimmunity.
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PMID:Relationship between CD5+ B lymphocytes and the activity of systemic autoimmunity. 169 88

Another autoimmune disease was found to accompany insulin dependent diabetes mellitus (IDDM) in 14% of the young diabetics (n = 14) studied. Thyroid autoimmune disease was the most common of the accompanying autoimmune diseases, and was detected in 11% (n = 15) of the patients. Two thirds of the IDDM patients with autoimmune thyroiditis were hypothyroid, one was hyperthyroid, and 20% lacked detectable thyroid antibodies when thyroid disease was diagnosed. Coeliac disease was found in 2% of the patients, and one had Addison's disease. Autoantibodies were found in one third of the patients. Thyroid microsomal antibodies were detected in 22% of the patients, IgA anti-gliadin in 11%, gastric parietal cell antibodies in 3% and rheumatoid factor in 7%. Autoimmune disease and the relevant autoantibodies coexisted in 11% of the patients. Autoimmune disorders and autoantibodies were not associated to any particular HLA type. The distribution of the HLA-types in the patients was unusual in that the frequency of HLA-DR3 was not increased. The value of autoantibody tests in the diagnosis of functional disorders of the thyroid and of coeliac disease are discussed.
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PMID:Autoantibodies and autoimmune diseases in young diabetics. 213 5

Islet cell antibodies (ICAs) in Chinese (23 IDDM, 13 NIDDM and 6 non-diabetic) were characterized for immunoglobulin isotypes and light chain specificity. All ICAs were IgG-type and none were IgM- or IgA-type (median titre: 20 JDF units; range 10-160). Light chain specificity showed that 25/36 (69.4%) of the diabetic patients had lambda and kappa chains. Half of the non-diabetic subjects had both lambda and kappa chains. The rest had only lambda chains. Isotyping for ICA-IgG subclass combination with IUIS/WHO reference monoclonal antibodies in the diabetic patients gave the following: IgG1 alone-9 (25%), IgG1+2+3-8 (22.2%), IgG1+2-11 (30.6%), IgG1+3-6 (16.7%), IgG2+3-2 (5.6%). No ICA-IgG4 was detected. The frequency of the subclasses would be: IgG1-94.4%, IgG2-58.3% and IgG3-44.4%. The distribution of ICA-IgG subclasses was not affected by diabetes type (IDDM or NIDDM) or duration of disease. Of the 6 non-diabetic subjects only one had a single ICA-IgG subclass (IgG1). Serum levels of IgG subclasses in a subgroup of the patients (n = 16) were not significantly different from normal individuals. Biochemical modification of pancreatic tissue prior to ICA testing showed that acetylneuraminic acid residues, lipid and protein components were associated with binding of ICAs. The co-existence of other autoantibodies was also tested in these 42 ICA-positive sera. Twelve individuals (1 non-diabetic) had thyroid autoantibodies. Antibodies to thyrotrophin receptor, gastric parietal cell and rheumatoid factor were not detected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Non-restricted immunoglobulin-G subclass islet cell antibodies in Chinese. 813 59

The tyrosine phosphatase PTPN22 allele 1858T has been associated with rheumatoid arthritis (RA) and other autoimmune diseases. RA is the most frequent of those multifactorial diseases. The RA association was usually restricted to serum rheumatoid factor positive disease (RF+). No interaction was shown with HLA-DRB1, the first RA gene. Many case-control studies replicated the RA association, showing an allele frequency increase of approximately 5% on average and large variations of population allele frequencies (2.1-15.5%). In multifactorial diseases, the final proof for a new susceptibility allele is provided by departure from Mendel's law (50% transmission from heterozygous parents). For PTPN22-1858T allele, convincing linkage proof was available only for type 1 diabetes. We aimed at providing this proof for RA. We analyzed 1,395 West European Caucasian individuals from 465 "trio" families. We replicated evidence for linkage, demonstrating departure from Mendel's law in this subset of early RA onset patients. We estimated the overtransmission of the 1858T allele in RF+ families: T = 63%, P < 0.0007. The 1858T allele frequency increased from 11.0% in controls to 17.4% in RF+ RA for the French Caucasian population and the susceptibility genotype (1858T/T or T/C) from 20.2% to 31.6% [odds ratio (OR) = 1.8 (1.2-2.8)]. In conclusion, we provided the linkage proof for the PTPN22-1858T allele and RF+ RA. With diabetes and RA, PTPN22 is therefore a "linkage-proven" autoimmunity gene. PTPN22 accounting for approximately 1% of the RA familial aggregation, many new genes could be expected that are as many leads to definitive therapy for autoimmune diseases.
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PMID:Linkage proof for PTPN22, a rheumatoid arthritis susceptibility gene and a human autoimmunity gene. 1723 19

An important feature of autoimmune diseases is the overlap of pathophysiological characteristics. Clustering of autoimmune diseases in families suggests that genetic variants may contribute to autoimmunity. The aim of the present study was to investigate the role of the interferon induced with helicase domain 1 (IFIH1) A946T (rs1990760 A>G) variant in rheumatoid arthritis (RA), as this was recently associated with susceptibility to type 1 diabetes. A total of 965 Caucasians with RA and 988 healthy controls were genotyped for IFIH1 A946T. Gene expression of IFIH1 was measured in peripheral blood leukocytes using real-time PCR. Genotypes were equally distributed in both RA cases and healthy controls (odds ratio for allele C = 0.9, 95% confidence interval = 0.8-1.0, P = 0.3). No association was detected after stratification by sex, age at onset, rheumatoid factor status, anti-cyclic citrullinated peptide status or radiological joint damage. Levels of IFIH1 mRNA were approximately twofold higher in blood leucocytes of RA cases compared with healthy controls (P < 0.0001). These results indicate that the IFIH1 is upregulated in RA but that the A946T variant does not contribute significantly to the genetic background of RA.
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PMID:The interferon induced with helicase domain 1 A946T polymorphism is not associated with rheumatoid arthritis. 1744 11

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive disorder typically presenting with chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal failure variably accompanied by other symptoms. APECED is caused by a mutation in the autoimmune regulator gene (AIRE). Today over 60 different mutations are known world-wide, most of them localized in exons 2, 8, and 10. We report here a German girl with rheumatoid factor positive arthritis, chronic mucocutaneous candidiasis, autoimmune hepatitis, chronic diarrhea, vitiligo, hypothyroidism, hypoparathyroidism, and adrenal failure who is homozygous for a novel mutation at the end of exon 3 of the AIRE gene (c.462G>A), within the conserved splice donor sequence. This mutation probably introduces a frameshift after amino acid 154 (p.Pro154fs) by skipping exon 4. In addition, we analyzed five other family members out of three generations for the AIRE gene mutation and for polymorphisms in the cytotoxic T lymphocyte antigen 4 (CTLA4) gene region and lymphoid protein tyrosine phosphatase (PTPN22) gene, which are associated with the occurrence of sporadic autoimmune Addison's disease, type 1 diabetes mellitus, and generalized vitiligo.
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PMID:Novel homozygous AIRE mutation in a German patient with severe APECED. 1920 22

Human parvovirus B19 is a single-stranded DNA virus which preferentially targets the erythroblasts in the bone marrow. B19 infection commonly causes erythema infectiosum, arthralgia, fetal death, transient aplastic crisis in patients with shortened red cell survival, and persistent infection in people who are immunocompromised. Less common clinical manifestations include atypical skin rashes, neurological syndromes, cardiac syndromes, and various cytopenias. B19 infection has also been associated with development of a variety of different autoimmune diseases, including rheumatological, neurological, neuromuscular, cardiovascular, haematological, nephrological and metabolic. Production of a variety of autoantibodies has been demonstrated to occur during B19 infection and these have been shown to be key to the pathogenesis of the particular disease process in a significant number of cases, for example, production of rheumatoid factor in cases of B19-associated rheumatoid arthritis and production of anti-glutamic acid decarboxylase (GAD) in patients with B19-associated type 1 diabetes mellitus. B19 infection has also been associated with the development of multiple autoimmune diseases in 12 individuals. Documented mechanisms in B19-associated autoimmunity include molecular mimicry (IgG antibody to B19 proteins has been shown to cross react with a variety of recognised human autoantigens, including collagen II, keratin, angiotensin II type 1 receptor, myelin basic protein, cardiolipin, and platelet membrane glycoprotein IIb/IIIa), B19-induced apoptosis with presentation of self-antigens to T lymphocytes, and the phospholipase activity of the B19 unique VP1 protein.
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PMID:The role of parvovirus B19 in the pathogenesis of autoimmunity and autoimmune disease. 2664 21

Type 1 diabetes mellitus (DM) and rheumatoid arthritis (RA) have been reported to occur concurrently in some cases. This study aimed to evaluate the presence of anti-cyclic citrullinated peptide (CCP) antibodies, which have been reported to have diagnostic value for RA, in children with type 1 DM. The study included 90 children with type 1 DM (Group 1) and 76 control cases (Group 2). The rates of reported family histories of RA and rheumatoid factor positivity did not differ between groups. In group 1, one case (1.1%) was positive for anti-CCP antibodies, whereas none of the controls were positive. The anti-CCP positive patient had no relevant joint complaints. Anti-CCP antibodies were rarely found in cases of pediatric type 1 DM. Thus, relevant screening in the follow-up of pediatric patients does not appear to be rational in the absence of any signs or symptoms of arthritis. The single case exhibiting a high anti-CCP level needs to be followed up for RA, although this positive result might be nonspecific and transient.
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PMID:Anti-cyclic citrullinated peptide antibodies are not frequently observed in children with type 1 diabetes mellitus: a single-center study. 2827 12

Nivolumab, an anti-programmed cell death 1 antibody, has been approved for the treatment of unresectable advanced non-small-cell lung cancer (NSCLC). Although immune-related adverse events (irAEs) such as dermatologic, digestive, endocrine, hepatic, and pulmonary toxicities are known to occur upon administration of immune checkpoint inhibitors, case reports of polymyalgia rheumatica (PMR) associated with nivolumab use are rare. We report a case of an NSCLC patient who developed PMR during treatment with nivolumab and received corticosteroids. A 74-year-old man without a history of autoimmune diseases received nivolumab at a dosage of 3 mg/kg once every 2 weeks for the treatment of stage IIIB squamous cell carcinoma. After 12 cycles of nivolumab treatment, he developed grade 3 muscle pain and arthralgia, requiring hospitalization and discontinuation of nivolumab. A bone scintigraphy revealed no bone metastasis. Serological tests showed that although creatine phosphokinase did not increase, C-reactive protein and the erythrocyte sedimentation rate were both high. Tests for the rheumatoid factor, anti-cyclic citrullinated peptide antibody, and anti-nuclear antibody were negative. In addition to the serological findings, joint ultrasonography data and clinical symptoms were evaluated, leading to the diagnosis of PMR. Oral prednisolone 20 mg/d was started to treat the PMR without giant-cell arteritis. The patient's symptoms improved within 5 d of the initiation of treatment. Prednisolone was tapered to 5 mg/d without recurrence of PMR. Although grade 3 or 4 irAEs (except in type 1 diabetes) are generally treated with high-dose corticosteroids, grade 3 PMR associated with nivolumab use may be treatable with low-dose corticosteroids.
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PMID:[Effectiveness of a Low-dose Corticosteroid in a Patient with Polymyalgia Rheumatica Associated with Nivolumab Treatment]. 3082 27