Histocompatibility antigens (HLA) and patterns of cognitive loss in dementia of the Alzheimer type

Recent data suggest that a proportion of patients with primary neuronal degeneration of the Alzheimer type have the HLA-B7 antigen. However, the possibility that other differences might exist between patients with and without the marker has not been examined. We tested a range of cognitive skills in Alzheimer patients with and without the HLA-B7 to examine whether those individuals with the HLA marker would exhibit a profile of cognitive loss different from those without it. Our results indicate that patients with HLA-B7 antigens had selective attentional scores that were significantly lower than Alzheimer patients without the antigen. Neither group was significantly different in either memory capacity or retrieval from short-term and long-term memory. The data support the hypothesis that there may be more than one disorder in what is now referred to as dementia of the Alzheimer type.     

Histocompatibility antigens (HLA) and patterns of cognitive loss in dementia of the Alzheimer type

Recent data suggest that a proportion of patients with primary neuronal degeneration of the Alzheimer type have the HLA-B7 antigen. However, the possibility that other differences might exist between patients with and without the marker has not been examined. We tested a range of cognitive skills in Alzheimer patients with and without the HLA-B7 to examine whether those individuals with the HLA marker would exhibit a profile of cognitive loss different from those without it. Our results indicate that patients with HLA-B7 antigens had selective attentional scores that were significantly lower than Alzheimer patients without the antigen. Neither group was significantly different in either memory capacity or retrieval from short-term and long-term memory. The data support the hypothesis that there may be more than one disorder in what is now referred to as dementia of the Alzheimer type.     

Histocompatibility antigens in progressive systemic sclerosis (PSS; scleroderma)

Patients with progressive systemic sclerosis (PSS; scleroderma) were typed for the HLA-A, -B, and -DR antigens. No significant differences in the frequencies of any HLA-A or -B antigen were found. In the subgroup of patients with PSS and diffuse scleroderma (PSS-DS), the frequency of Bw35 was increased (0.30 vs 0.17 in controls;P<0.005, correctedP>0.2). Although patients with PSS-DS also had an increased frequency of DR1 antigen (0.27 vs 0.12 in local controls;P<0.005, correctedP<0.05), no association between Bw35 and DR1 antigens could be detected. We found no increase in the frequencies of the DR3 or DR5 antigens in patients with PSS. However, in a subset of PSS patients with pulmonary fibrosis, an increase in DR3 and a decrease in DR4 antigens (P<0.005) were observed. Serum antibodies to centromere occurred more frequently in DR1-positive than DR1-negative patients (0.46 vs 0.18;P<0.005). This study of a large number of patients with PSS failed to confirm previously reported associations of PSS with the HLA-B8/DR3 haplotype or HLA-DR5 antigen.     

HLA antigens in sarcoidosis.

The HLA antigens were identified in sixty-five patients with sarcoidosis, comprising forty-five with uveitis, twelve with erythema nodosum and eight with arthritis. In the group with arthritis, B8 was present in seven of eight (P = 0-0016) and the haplotype 1,8 in five of eight (P = 0-0053). A1 was present in 44% with uveitis (P = 0-04). There was no other significant disturbance of antigen frequencies in uveitis or in erythema nodosum, but it was noteworthy that B27 was present in only two patients with uveitis.     

Histocompatibility antigens and natural killer susceptibility

The central question of the nature of the structure(s) involved in the recognition of targets by natural killer (NK) cells remains unresolved. Although NK-mediated cytotoxicity is not MHC-restricted, it has been suggested that these cells could recognize the targets more effectively in the absence of MHC class I antigens. In this paper we review the contradictory results obtained when studying the NK susceptibility of cell lines which constitutively express different levels of MHC antigens, or which have been induced to express MHC antigens by gene transfection or gamma-interferon treatment. Taken together, the results indicate that MHC antigens play a differential role in NK lysis depending on the nature of the target cells used; MHC class I antigens play a role in the NK resistance of cells from a hematopoietic lineage, but this does not extend to cells from other origins. The data reviewed also support the hypothesis that MHC class I antigens induced NK resistance by interfering with target structures, and that multiple NK molecules are involved in NK-mediated lysis as part of a possible advanced recognition system.     

Human lymphocyte antigens (HLA) and Graves' disease in Turkey

To evaluate the association of HLA types with Turkish patients with Graves' disease, HLA typing, clinical findings, and thyroid antibodies were correlated. The HLA types, clinical findings (ophthalmopathy and age at onset), and thyroid stimulating hormone (TSH) receptor (TRAb) and antithyroid microsomal antibodies (MAb) were analyzed. Seventy Turkish patients with Graves' disease and 306 control subjects were assessed. Serological HLA typing was performed in HLA A, B, C, DR, and DQ loci. There was a significantly increased prevalence of HLA B8, B49, DR3, DR4, and DR10 in Graves' disease. The association of Graves' disease with HLA DR3 was found to be less strong than previously described. The HLA DR4 antigen may contribute to the predisposition of Graves' disease in Turkey. The results suggest that HLA B7, B13, DR7, DQw2, and DQw3 may confer a protective effect for Graves' disease in Turkey. Patients carrying HLA B12, B18, and B44 haplotypes had a tendency to develop the disease at a later age. The difference from the other studies may be the result of the selection of the controls; in part, of the variability in serological typing reagents; and, also, of the rather weak HLA associations with the disease.This study was presented in part at the Annual Meeting of the National Endocrinology and Diabetes Association, Bursa, Turkey, May 25–28, 1992.     

HLA antigens in pernicious anaemia.

The increased frequency of HLA-B7 alone and HLA-A3/B7 together, in the same patient, has been confirmed in pernicious anaemia. There is no increase prevalence of HLA-A3 alone. No association has been found between the presence of serum intrinsic factor type 1 antibody and HLA-A3 or HLA-B7.     

Morphogenesis of diabetic microangiopathy]

Skin biopsies from 40 patients 17 to 75 years old with type I and II diabetes mellitus were studied morphologically. The formation of diabetic microangiopathy starts with the damage of endotheliocytes, vascular permeability disturbance, activation of pericytes and smooth muscle elements with subsequent thickening of basal membranes and capillary and arteriole hyalinosis, these lesions being directly related to the duration of diabetes. Diabetic microangiopathy is a manifestation of the disease and its morphology is similar in both type I and II diabetes.