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Jerry Palmer

Publications and source records attributed to Jerry Palmer.

6 recordsLinked to original sources
PubMed2006

MHC class I chain-related gene-A is associated with IA2 and IAA but not GAD in Swedish type 1 diabetes mellitus.

In type 1 diabetes mellitus (T1DM), the frequency of antibodies against insulin (IAA), glutamic acid decarboxylase-65 (GAD65), ICA512/IA2 (IA2), and islet cell antigens (ICA) vary with human leukocyte antigen (HLA) composition of the patient. IAA, IA2 autoantibodies, and ICA are increased in DQ8 positives; GAD65 antibodies are increased in DQ2 positives. MHC class I chain-related gene-A (MICA) is another genetic marker that has been proposed to be associated with T1DM. In this article, we looked at microsatellite polymorphism of MICA and its association with autoantibodies (IAA, IA2, and GAD65) in Swedish T1DM patients and if the association explains its importance in early events in autoimmune response. We studied 635 T1DM patients between 0-35 years. Frequency of MICA5/5 was positively associated with the formation of IAA and IA2 antibodies considered individually or in combination (odds ratio [OR], 95% CI, Pc: [IAA+ versus IAA-]: 4.94, 2.09-11.62, <0.0005; [IA2+ versus IA2-]: 2.65, 1.52-4.59, 0.0015; [IAA and/or IA2+ versus rest]: 9.83, 2.37-40.78, <0.0015; [IAA and IA2+ versus rest]: 3.51, 2.01-6.15, <0.0015). Also, -5.1/5.1 was increased in IAA+ patients compared to IAA- patients (2.82, 1.64-4.83, <0.0005). All patients positive for -5/5 developed at least one of the three antibodies. Frequency of MICA5.1 was decreased in IAA+ (0.54, 0.36-0.81, 0.017), in IA2A+ (0.63, 0.45-0.88, 0.04), in IAA and/or IA2A+ (0.52, 0.33-0.84, 0.044), and in IAA and IA2A+ (0.55, 0.39-0.78, 0.0055) patients when compared with patients negative for corresponding antibodies. Frequency of MICA9, 5/5.1, and 5.1/9 was decreased in IAA+ compared to IAA- patients (0.51, 0.32-0.79, 0.021; 0.22, 0.11-0.44, <0.005; and 0.39, 0.22-0.69, 0.026, respectively). Frequency of MICA9 and -5.1/9 was also decreased in IAA and/or IA2 antibody-positive patients while MICA5/5.1 decreased in patients positive for IAA and IA2 antibody both together. IAA and IA2 antibodies are believed to appear early during the autoimmune reaction against beta cells. Thus, according to our data, MICA-5/5 and -5.1/5.1 is associated with early autoimmunity in T1DM patients. Our study suggests that MICA gene polymorphism is associated with autoantibody formation and that the polymorphism especially MICA5/5 and -5.1/5.1 are important in early events of autoimmune reaction.

Adolescent↗
PubMed2003

Recombinant Fabs of human monoclonal antibodies specific to the middle epitope of GAD65 inhibit type 1 diabetes-specific GAD65Abs.

Autoantibodies to the 65-kDa isoform of GAD (GAD65Abs) are associated with type 1 diabetes development, but the conformational nature of the GAD65Ab epitopes complicates the evaluation of disease risk. Six GAD65-specific recombinant Fabs (rFabs) were cloned from monoclonal antibodies b96.11, DP-C, DP-A, DPD, 144, and 221-442. The binding of GAD65Abs in 61 type 1 diabetic patients to GAD65 was analyzed by competitive radioimmunoassays with the six rFabs to ascertain disease-specific GAD65Ab binding specificities. The median binding was reduced significantly by rFab b96.11 (72%) (P < 0.0001), DP-A (84%) (P < 0.0001), DP-C (84%) (P < 0.0001), 221-442 (79%) (P < 0.0001), and DP-D (80%) (P < 0.0001). The competition pattern in type 1 diabetic patients differed from that in GAD65Ab-positive late autoimmune diabetes in adults (LADA) patients (n = 44), first-degree relatives (n = 38), and healthy individuals (n = 14). Whereas 87 and 72% of the type 1 diabetic sera were competed by rFab b96.11 and DP-C, respectively, only 34 and 26% of LADA patients, 18 and 25% of first-degree relatives, and 7 and 28% of healthy individuals showed competition (P < 0.0001). These findings support the view that type 1 diabetes is associated with disease- and epitope-specific GAD65Abs and supports the notion that the middle epitope is disease associated. These GAD65-specific rFabs should prove useful in predicting type 1 diabetes and in the study of conformational GAD65Ab epitopes.

Adolescent↗
PubMed2002

Declining beta-cell function in type 2 diabetes: 5-year follow-up and immunologic studies of the population of Wadena, MN.

The aim of the study was to describe 5-year changes in meal-stimulated pancreatic insulin reserve in adults with normal and impaired glucose tolerance (NGT, IGT) and diabetes, with or without islet-related antibodies. This was a 5-year follow-up of 270 residents of Wadena, MN, of northern European origin, with good kidney function, defined as creatinine clearance greater than 60 mL/min/1.73 m(2). The subjects comprised a population-based sample originally studied in 1986 to 1987. Urine C-peptide (CP), in a 260-minute collection, was the integrated measure of insulin secretion; Ensure-Plus (Ross, Columbus, OH) was the liquid meal. Islet cytoplasmic antibodies (ICA), insulin autoantibodies (IAA), and glutamate decarboxylase antibodies (GAD65ab) were measured. In 182 subjects with NGT, there was no mean within-subject change in urine CP over 5 years (P =.34). In 41 subjects with impaired GT (IGT), there was a moderate, but nonsignificant, increase in mean CP, and 6 (15%) subjects increased. In 37 type 2 diabetic subjects not taking insulin (type 2-No Ins), who had a mean diabetes duration at the 5-year examination of 9.6 +/- 6.3 years, there was a 21% decrease in mean urine CP (P =.012), attributable mostly to a major drop in 8 of the 37 subjects (22%). Islet-related antibody tests were mostly negative; GAD65ab positivity was related to CP decline only among insulin-taking subjects. In summary, in Wadena adults, meal-stimulated urine CP was stable or increased over 5 years in subjects with NGT and IGT, but CP decreased significantly in about one fifth of type 2-No Ins subjects, with no relation to antibody test results.

Adult↗