Autoimmunity in Endocrine Disease

Irvine, W. J.

doi:10.1016/b978-0-12-571136-4.50020-6

Cited by 33 publications

(22 citation statements)

References 127 publications

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“…Unaffected relatives of diabetics have been found to have higher than expected prevalence of islet cell and other organ specific antibodies. 5 However, the prevalences reported have always been below 10%, much lower than those reported here for nucleic acid antibodies. High prevalence of extracellular membrane depositions of albumin in unaffected relatives of diabetics has also been reported by us.…”

Section: Discussionmentioning

confidence: 51%

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Prevalence of Antibodies to Nucleic Acids in Insulin-dependent Diabetics and Their Relatives

et al. 1981

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SUMMARYWe have studied nucleic acid antibodies in 23 insulindependent diabetics, 27 of their first degree relatives, and 23 normal, unrelated controls. We have found a significantly increased prevalence of antibody to ss-DNA, ds-RNA (reovirus), and synthetic RNA (Poly A Poly U, Poly I Poly C) in the unaffected relatives as well as in the diabetics when compared with normal controls. There was no relationship in HLA. DIABETES 30:873-874, October 1981. R ecently, we reported a high prevalence rate of antibodies against nucleic acids in insulin-dependent diabetic (IDD) patients in contrast to agematched and non-age-matched controls.1 The high titers of antibody, especially to double stranded (ds-) RNA, appeared to be related to the recent onset of illness. We speculated that an immune response might have taken place against viral agents implicated in beta-cell damage after a varying incubation period. In general, antibody titers seemed to fall in most cases after several years of illness, but some patients seemed to retain high antibody titers even after IDD for 5 yr. These observations prompted us to screen for these antibodies in the nondiabetic members of HLA (histocompatibility) tissue typed families with two or more IDD sibs with varying duration of illness. We also searched for associations of the antibody titers with sex, HLA haplotypes, and several clinical features. METHODSPatients. Twenty-three IDD patients (ages 9-34 yr, 12 males) from 12 families with at least 2 IDD sibs participating in the Minnesota Diabetes Genetic Study were tested. Pa-

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Section: Discussionmentioning

confidence: 51%

“…Both the albumin deposition 6 and the islet cell antibodies 5 have been reported to be associated with HLA. Our inability to find a relationship between nucleic acid antibodies and HLA may reflect either small sample size or an absence of association.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Antibodies to Nucleic Acids in Insulin-dependent Diabetics and Their Relatives

et al. 1981

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“…At the ultrastructural level, the antigen is localized to the cell membrane forming the microvilli of the parietal cells, a part of the cell suggested to play a role in the production of hydrochloric acid (7). Many patients (40-60%) with pernicious anemia, due to autoimmune gastritis, also have antibodies against intrinsic factor ( 17), a glycoprotein secreted by the parietal cells. The experiments of the present investigation demonstrated the ability of porcine vesicular membranes to inhibit the majority of antibody binding to gastric mucosa cell lysates.…”

Section: Resultsmentioning

confidence: 99%

Major parietal cell antigen in autoimmune gastritis with pernicious anemia is the acid-producing H+,K+-adenosine triphosphatase of the stomach.

Karlsson¹,

Burman²,

Lööf³

et al. 1988

J. Clin. Invest.

201

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In autoimmune gastritis antibodies against a membrane-bound parietal cell antigen of previously unknown function are present in the sera of patients. In this study, a vesicular membrane preparation of porcine gastric mucosa cells was found to be a potent antigenic source. This preparation blocked > 90% of antibody binding to a lysate of gastric mucosa cells. The membrane fraction contained H+,K+-ATPase (EC 3.6.136) as the major protein, which in sodium dodecyl sulfate-polyacrylamide gel electrophoresis migrated with a weight of 92 kD.After reduction and alkylation, this component was resolved into two bands of similar staining intensity (92 and 88 kD). Immunoblotting analysis showed that sera of patients recognized antigen with pattern identical to the major protein of the vesicular membranes.Protein A-Sepharose beads preincubated with immunoglobulins of five individual patient (but not control) sera were all found to reduce both the H+,K+-ATPase activity and the amount of parietal cell antigen of a preparation of vesicular membranes solubilized in n-octylglucoside. Taken together, the results of this study indicate that the major parietal cell antigen is identical to the acid-producing enzyme, H+,K+-ATPase, of the parietal cell.

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“…Monoclonal antibodies reactive with multiple organs, including the islets of Langerhans, have been previously produced by fusion ofsplenic leukocytes from reovirus Type I infected mice (40, 41) with mouse myeloma cells, or by fusion of peripheral blood lymphocytes from patients with insulin-requiring diabetes mellitus and other autoimmune abnormalities with mouse or human myeloma cells (42). It remains to be shown, however, whether extrapolation of these observations, and our findings that at least one antigenic determinant is present on cell surfaces in multiple endocrine organs, provide an explanation for circulating antibodies that have multiple organ reactivity and that are found in some patients with recent-onset diabetes mellitus (43,44). …”

Section: Discussionmentioning

confidence: 97%

A ganglioside antigen on the rat pancreatic B cell surface identified by monoclonal antibody R2D6.

Alejandro¹,

Shienvold²,

Hajek³

et al. 1984

J. Clin. Invest.

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Abstract. In an attempt to identify B cell specific antigens, we have generated a mouse monoclonal antibody, R2D6, which is directed against plasma membranes of rat pancreatic B ofthe DME, developed in 60:40:9 chloroform/methanol/ 2.5 N ammonia, Ag(R2D6) migrated with a relative mobility (Rf) of 0.54±0.07 (n = 3), which was a position nearly coincident with the purified brain ganglioside, GD1a. The antigen bound to DEAE-Sephacel, was not inactivated by mild treatment with base (which hydrolyzes phospholipids) and eluted in ganglioside fractions upon C18 Sep-Pak and upon silicic acid chromatography. Hence, the solubility characteristics, enzyme sensitivities, and behavior of Ag(R2D6) in four chromatography systems are consistent with its identification as a ganglioside.

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Autoimmunity in Endocrine Disease

Cited by 33 publications

References 127 publications

Prevalence of Antibodies to Nucleic Acids in Insulin-dependent Diabetics and Their Relatives

Prevalence of Antibodies to Nucleic Acids in Insulin-dependent Diabetics and Their Relatives

Major parietal cell antigen in autoimmune gastritis with pernicious anemia is the acid-producing H+,K+-adenosine triphosphatase of the stomach.

A ganglioside antigen on the rat pancreatic B cell surface identified by monoclonal antibody R2D6.

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