scholarly journals Humoral and cellular immune parameters before and during immunosuppressive therapy of a patient with stiff-man syndrome and insulin dependent diabetes mellitus

1998 ◽  
Vol 65 (2) ◽  
pp. 204-208 ◽  
Author(s):  
M Hummel ◽  
I Durinovic-Bello ◽  
E Bonifacio ◽  
V Lampasona ◽  
J Endl ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Immunosuppressive Therapy ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Immune Parameters ◽  
Insulin Dependent ◽  
Stiff Man Syndrome ◽  
Cellular Immune

scholarly journals Higher autoantibody levels and recognition of a linear NH2-terminal epitope in the autoantigen GAD65, distinguish stiff-man syndrome from insulin-dependent diabetes mellitus.

1994 ◽  
Vol 180 (2) ◽  
pp. 595-606 ◽  
Author(s):  
J Kim ◽  
M Namchuk ◽  
T Bugawan ◽  
Q Fu ◽  
M Jaffe ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
T Cells ◽  
Cd4 T Cells ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Cytotoxic T Cell ◽  
Dependent Diabetes Mellitus ◽  
Western Blots ◽  
Insulin Dependent ◽  
Stiff Man Syndrome

The smaller form of the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD65) is a major autoantigen in two human diseases that affect its principal sites of expression. Thus, destruction of pancreatic beta cells, which results in insulin-dependent diabetes mellitus (IDDM), and impairment of GABA-ergic synaptic transmission in Stiff-Man syndrome (SMS) are both characterized by circulating autoantibodies to GAD65. Anti-GAD65 autoantibodies in IDDM are predominantly directed to conformational epitopes. Here we report the characterization of humoral autoimmune responses to GAD65 in 35 SMS patients, of whom 13 (37%) also had IDDM. All SMS patients immunoprecipitated native GAD65 and the main titers were orders of magnitude higher than in IDDM patients. Furthermore, in contrast to the situation in IDDM, autoantibodies in 35 of 35 (100%) of SMS patients recognized denatured GAD65 on Western blots. Two major patterns of epitope specificity were identified on Western blots. The first pattern, detected in 25 of 35 SMS patients (71%), of whom 11 had IDDM (44%), was predominantly reactive with a linear NH2-terminal epitope residing in the first eight amino acids of GAD65. Nine of nine individuals who were HLA-haplotyped in this group carried an IDDM susceptibility haplotype and HLA-DR3, DQw2 was particularly abundant. The second pattern, detected in 10 of 35 patients (29%) of whom two had IDDM (20%), included reactivity with the NH2-terminal epitope plus strong reactivity with one or more additional epitope(s) residing COOH-terminal to amino acid 101. The second epitope pattern may represent epitope spreading in the GAD65 molecule, but may also include some cases of epitope recognition associated with IDDM resistant HLA-haplotypes. The principal NH2-terminal linear epitope in GAD65 distinguishes the reactivity of SMS and IDDM autoantibodies and may be a determinant of pathogenicity for GABA-ergic neurons. The greater magnitude and distinct specificity of the humoral response to GAD65 in SMS may reflect a biased involvement of the T helper cell type 2 (Th2) subset of CD4+ T cells and antibody responses, whereas IDDM is likely mediated by the Th1 subset of CD4+ T cells and cytotoxic T cell responses.

The insulin-dependent diabetes mellitus-associated ICA 105 autoantigen in stiff-man syndrome patients

1996 ◽  
Vol 69 (1-2) ◽  
pp. 129-134 ◽  
Author(s):  
Gianvito Martino ◽  
Luigi M.E. Grimaldi ◽  
Elena Bazzigaluppi ◽  
Nadia Passini ◽  
Francesco Sinigaglia ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Insulin Dependent ◽  
Stiff Man Syndrome

scholarly journals Azathioprin effect on immunologic parameters of patients with newly detected insulin-dependent diabetes mellitus

1993 ◽  
Vol 39 (5) ◽  
pp. 16-20
Author(s):  
M. Sh. Shamkhalova ◽  
I. A. Abugova ◽  
P. I. Shishko ◽  
I. I. Dedov ◽  
L. V. Kozlov ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Immunosuppressive Therapy ◽  
Cell Function ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
T Helper ◽  
Cell Counts ◽  
Insulin Dependent ◽  
Male Patients

Azathioprin immunosuppressive therapy prolongs remissions and stimulates residual p-cell function, suppresses insulin antibody production, reduces the activity of the complement and CH50 components, reduces initially increased cellular immunity parameters (total T and В cell counts, T helper to T inductor ratio, and the count of DR carrier cells) in patients with newly detected insulin-dependent diabetes mellitus; this makes this drug effective at the firts stages of the disease. When selecting patients for immunosuppressive therapy the following immunity parameters should be examined: complement status, total counts of T and В lymphocytes, T-helper-in- ductor/T-suppressor-cytotoxic immunoregulation index, DR carrier cell counts. Reduced levels thereof are a contraindication against immunosuppressant therapy. Male patients with insulindependent diabetes mellitus debut at the age of over 25 are particularly susceptible to immunosuppressive therapy with azathioprin.

Cellular immune abnormalities and autoreactive T lymphocytes in insulin-dependent diabetes mellitus in rats

1985 ◽  
Vol 6 (5) ◽  
pp. 160-162 ◽  
Author(s):  
Gérald J. Prud'homme ◽  
Eleanor Colle ◽  
Abraham Fuks ◽  
Audrey Goldner-Sauve ◽  
Ronald D. Guttmann
Keyword(s):  
Diabetes Mellitus ◽  
T Lymphocytes ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Insulin Dependent ◽  
Cellular Immune

Elevated Circulating P-Selectin in Insulin Dependent Diabetes Mellitus

1996 ◽  
Vol 76 (03) ◽  
pp. 328-332 ◽  
Author(s):  
Bernd Jilma ◽  
Peter Fasching ◽  
Christine Ruthner ◽  
Anna Rumplmayr ◽  
Sabine Ruzicka ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Plasma Levels ◽  
Plasma Concentrations ◽  
Insulin Dependent Diabetes Mellitus ◽  
Interquartile Range ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Intergroup Comparison ◽  
Median Plasma ◽  
Insulin Dependent

SummaryBased on findings that showed increased P-selectin expression on platelets and on choroidal microvessels of patients with insulin dependent diabetes mellitus (IDDM), we hypothesized that also plasma concentrations of circulating (c)P-selectin would be increased in these patients.The aim of this study was to compare the plasma levels of cP-selec-tin between non-smoking patients with IDDM, treated with an intensified insulin therapy, and healthy controls. The study design was prospective, cross-sectional and analyst-blinded. Subjects were matched individually for sex, age and body mass index. Plasma levels of cP-selectin and of von Willebrand antigen (vWF-Ag) were determined by enzyme linked immunoassays.Forty-two pairs were available for intergroup comparison. Median plasma concentrations of cP-selectin in patients with IDDM (285 ng/ml; interquartile range: 233-372) were on average 21% higher than those of controls (236 ng/ml; interquartile range: 175-296; p = 0.004). Also, median plasma levels of vWF-Ag were 10% higher in patients (96 U/dl; interquartile range: 82-127) than controls (87 U/dl; interquartile range: 70-104; p = 0.025). There was no correlation between plasma concentrations of cP-selectin and vWF-Ag levels in either group (p ώ0.05).In conclusion, our results of increased cP-selectin levels are in line with increased P-selectin expression on platelets and on choroidal microvessels found in patients with IDDM. In view of the currently developed small molecule inhibitors of cell adhesion molecules, these independent observations together may provide a sound rationale to select P-selectin as a target for treating or preventing IDDM-associated micro- or macrovascular complications.

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