Progesterone binding to lymphocytes-cause for transient loss of HLA antigens in women?

In 5 women with normal ovulation cycle the weakening to loss of lymphocyte HLA antigens was proved in most menstrual periods and in the interval between two menstruations, sometimes on days 20-23 of the genital cycle. In the intermenstrual period the increase of the progesterone level in the blood was found. The binding of progesterone on the lymphocyte surface seems to be the cause of the blocking of HLA antigens in the intermenstrual period.     

Human leucocyte antigens and mixed lymphocyte reaction in severe pre-eclampsia.

Human leucocyte antigens (HLA) and mixed lymphocyte reactions (MLR) were studied in 38 women with severe pre-eclampsia and their husbands. Thirty-nine women with normal pregnancies and their husbands served as controls. Thirty-three of the control women were matched for age and parity with members of the study group. Infants were studied when possible. HLA compatibility was increased in the pre-eclamptic group compared with matched controls and with theoretical estimates for possible matings. The one-way MLR at delivery showed diminished response of maternal to paternal and cord cells in pre-eclamptic women. This reduced maternal reactivity in women with pre-eclampsia may have a role in the illness, and paternal/maternal histocompatibility may be a feature of the severe form.     

Interesting relations in the HLA system

There exists no absolute binding between the antigens HLA-Cw 2, Cw 3 and Cw 4, on the one hand, and HLA-B 27, HLA-B 15 and HLA-Bw 35, on the other hand. Even if 91% of human beings with HLA Cw 4 will simultaneously have the antigen HLA-Bw 35, another antigen as HLA-B 27 or HLA-B 15 can be identified in approximately 55% of individuals with HLA-Cw 2 and Cw 3. In this connection, the joint presence of some pairs of cross-reacting HLA antigens (A 2 and A 28, B 5 and Bw 35, B 7 and B 27, B 8 and B 14, B 12 and Bw 2) could be proved and their frequency be determined. 2 cases of a simultaneous presence of two subtypes of HLA-A 10 antigen, A 25 and A 26, could be found in family examinations. Moreover, two atypical bindings of anti-HLA-Bw 4 and anti-HLA-Bw 6 cytotoxins with HLA antigens could be identified: 7,49% of HLA-Bw 35 positive lymphocytes no positive response with anti-HLA-B 4 and 1,69% of HLA-B 12 with anti-HLA Bw 6. The importance of the findings for determining HLA in practice is discussed.     

Distribution of HLA antigens in patients with meningococcal infection at different times of year

The character of the distribution of the antigens of the HLA system at different seasons has been studied in 160 patients with generalized forms of meningococcal infection. The occurrence of HLA-Bw16 (the marker of the population gene of susceptibility to meningococcal infection) has proved to be inversely correlated with the seasonal morbidity level.     

Modulation of HLA antigens in response to the binding of epidermal growth factor by A431 cells

In a previous study [(1984) J. Cell Biol. 98, 725-731] we showed that the level of human MHC, HLA antigens on A431 carcinoma cells is reduced after these cells bind epidermal growth factor (EGF). Here we use flow cytometry to determine the effects of various doses and times of EGF treatment on HLA expression. We then show that the reduction in HLA expression is associated with a reduction in the level of phosphorylation of immunoprecipitable surface HLA antigens, although longer exposure of cells with EGF increased both surface HLA expression and their phosphorylation levels. Lateral diffusion of HLA antigens is lower in EGF-treated than in control cells. The lower diffusion coefficients measured may be causally related to the decreased phosphorylation of HLA antigens.     

The problem of preparing avid cytotoxic anti-B-lymphocyte serums]

There were anti-B-lymphocyte toxins in 40 samples (= 7.58%) from 527 examined sera of pregnant women and polytransfused persons without HLA cytotoxins and 84 samples (= 33.2%) from 253 anti-HLA sera. Of 49 specific anti-B sera 27 were suitable for typing B-lymphocyte antigens; with the help of 13 of these sera 5 specific antigens of B-lymphocytes called 1-5 could be determined. These 27 sera produced a positive cytotoxic reaction, mainly with the strength of +++ or ++. Attempts of absorbing HLA antibodies from anti-B lymphocyte sera led to unsatisfactory results. Sometimes the content of anti-B-lymphocyte toxins could also be diminished by a platelet absorption, in other cases the absorption was insufficient and had to be repeated therefore.     

Immunologic phenomena in habitual abortion

12 women with recurrent abortions are investigated for various immunological parameters. Couples studied shared several HLA antigens, those women do not develop HLA' antibodies and cellular cytotoxicity against their husband. Their serum has an abnormal glycoprotein, migrating in the alpha globulin zone, precipitating with anti beta globulin serum. The women studied with recurrent abortions never possessed the Blocking Factor present in the serum of pregnant women, able to inhibit a cellular cytotoxicity reaction in vitro. It is proposed a reliable and simple test which could inform on the outcome of abortions.     

The transient loss of HLA antigens on lymphocytes in patients following administration of penicillin and tetracyclin.

Ten patients with inflammatory affections of urinary, respiratory and bile tract, as well as otitis patients were administered Penicillin. Six or seven days after the start of the treatment, four of them showed weakening or loss of minimally two earlier determined HLA antigens. The loss of HLA antigen was likewise demonstrated in a patient treated with Tetracycline. The HLA antigens were reliably demonstrated again six to seven days after the end of the treatment. The results suggest a possible false typing of HLA antigens in patients who had been administered Penicillin or Tetracycline. In accordance with Ben-David et al. [1] transient loss of two HLA antigens with concomitant development of lymphocyte polyreactivity was found in one of four patients treated with Chloramphenicol.     

Separation and comparison of human TL-like antigens and HLA(A,B, C) antigens expressed on Cultured T cells

Beta₂-microglobulin-bound T-cell membrane components containing both human TL-like antigens and HLA(A, B, C) antigens were partially purified from Renex 30-solubilized membrane material of cells of a human T-cell-type leukemia cell line, HPB-ALL. The radioiodinated preparation was subjected to limited papain digestion; the HLA(A, B, C) antigens split, whereas a large portion of the human TL-like antigens remained intact. The antigen molecules were recovered by lentil-lectin affinity chromatography and separated by gel filtration on the basis of the induced difference in molecular size. The human TL-like-antigen preparation thus obtained was essentially free of HLA(A, B, C) antigens. The human TL-like antigens were immunospecifically precipitated and the component polypeptide, heavy and light, chains were separated by acid dissociation followed by gel filtration. The component chains were compared with the corresponding chains of HLA(A, B, C) antigens obtained similarly from the same HPB-ALL cells with respect to their fragmentation patterns on chemical or enzymatic cleavage. The results provided convincing evidence for the identity of the light chains of human TL-like antigens and HLA(A, B, C) antigens, and also evidence suggesting the presence of substantial differences in the fundamental structure of the heavy chains of human TL-like antigens and HLA(A, B, C) antigens.A unit of the New York State Department of Health.     

The possible anti-inflammatory role of circulating human leukocyte antigen levels in women with endometriosis after treatment with danazol and leuprorelin acetate depot

BACKGROUND: Endometriosis is defined as an inflammatory condition of the female reproductive tract, a state often associated with infertility and miscarriage. Many exogenously administered factors (treatments) control the disease via as yet unknown pathways. Possible candidate molecules involved in these mechanisms could be the serum-soluble human leukocyte antigens (sHIA) that have been detected in a variety of human body fluids and that are associated with several diseases. AIMS: We here examine how danazol and leuprorelin acetate depot treatments exert their anti-inflammatory action. It is plausible that subtle alterations mediated by these treatments and in relation to sHLA may explain the pathophysiology of endometriosis and provide insights towards new therapeutic protocols. METHODS: Indirect enzyme-linked immunosorbent assay (ELISA), using specific monoclonal antibodies, determined serum-soluble class-I and class-II HLA levels. ELISA readings from treated women were compared with normal healthy subjects. RESULTS: Serum-soluble class-I and class-II HLA levels are statistically significantly lower (P < 0.001) in women with endometriosis than in the control groups. However, danazol but not leuprorelin acetate depot administration augments soluble HLA class I and class II (P < 0.01 and P < 0.001, respectively) to normal levels during the treatment period, an increase that may account for the anti-inflammatory effect and the remission observed. CONCLUSIONS: It is shown that one of the underlying causes of endometriosis may be the lack of both circulating class-I and class-II antigen levels. Danazol administration acts via an induced release of these antigens, whose presence correlates with the degree of the inflammatory alleviation obtained. We thus provide evidence that the inflammatory state of the disease appears to be associated with soluble HLA levels because, 3 months after ceasing therapy, the circulating antigens in the serum return to the same levels that correspond to the pathological condition.     

An adenovirus type 2 glycoprotein blocks cell surface expression of human histocompatibility class I antigens

The adenovirus type 2 encoded protein E3/19K binds to human histocompatibility class I antigens (HLA). This association occurs both in adenovirus-infected cells and in cells that have been transfected with the gene encoding the E3/19K protein. The formation of the HLA-E3/19K complex prevents the HLA antigens from being correctly processed by inhibiting their terminal glycosylation. This effect is specific for HLA antigens and does not generally involve the glycosyltransferases. Furthermore, the HLA-E3/19K association dramatically reduces the cell surface expression of the HLA antigens. This reduced level of antigens might influence the cytotoxic T cell response. Therefore, our results show a possible molecular mechanism whereby adenoviruses, and perhaps other viruses, delay or escape the cellular immune system of the host.     

Immunochemical and functional analysis of HLA class II antigens induced by recombinant immune interferon on normal epidermal melanocytes

The effect of recombinant immune interferon (IFN-gamma) on the expression and shedding of HLA antigens and of melanoma-associated antigens (MAA) by epidermal melanocytes was investigated by using serologic and immunochemical techniques. IFN-gamma enhances the expression and/or shedding of HLA class I antigens and of the cytoplasmic MAA defined by monoclonal antibody (MoAb) 465.12S and induces a slight reduction in the expression of the high m.w. melanoma-associated antigen (HMW-MAA). In agreement with the data in the literature, melanocytes incubated with IFN-gamma acquire HLA-DR, -DQ, and -DP antigens. Contrary to previous information in the literature, the effect is not restricted to HLA class II antigens, since IFN-gamma also induces the expression of the 96-kDa MAA recognized by MoAb CL203. The effect of IFN-gamma on HLA class II antigens and 96-kDa MAA is dose and time dependent and is specific, because recombinant leukocyte interferon affects the expression of neither type of antigen. In spite of the expression of HLA class II antigens, IFN-gamma-treated melanocytes do not acquire the ability to stimulate the proliferation of allogeneic lymphocytes. HLA-DR antigens are more susceptible to induction by IFN-gamma than HLA-DQ and -DP antigens, since the percentage of melanocytes acquiring HLA-DQ and -DP antigens is lower than that acquiring HLA-DR antigens. Furthermore, the dose of IFN-gamma is higher and the time of incubation is longer to induce HLA-DQ and -DP antigens than to induce HLA-DR antigens. The differential susceptibility of HLA-DR, -DQ, and -DP antigens as well as of melanocytes from various donors to the modulating effect of IFN-gamma may provide an explanation for the more frequent detection of HLA-DR than of HLA-DQ and -DP antigens in melanoma lesions and for the expression of HLA class II antigens by some, but not all, melanoma lesions.     

The impact of symbolism on immunogenetics: an application to HLA

The genes coding for the class I human lymphocyte antigens (HLA) are located on chromosome 6. These antigens are involved with the immunological interaction between cells. In some immunogenetic systems, such as HLA in humans, genes are defined by antibody/antigen reaction and are denoted by single symbolic identifiers. This symbolization assumes a one-to-one correspondence between antibodies, antigens and genes. Recent molecular studies, however, suggest that HLA antibody/antigen reaction is complex and most HLA class I specific antibodies may not uniquely identify a single allelic product. Where cross-reactivity is present in an immunogenetic system it is important to label each reagent with symbols corresponding to all genes coding for antigens with which the reagent will react. The problems of cross-reactive groups and unexplained linkage relations may be elucidated by the redefinition and clarification of certain HLA antigens. A computer program can suggest such labelling schemes using input given by phenotype reaction patterns with a panel of reagents. When this program was applied to data on the class I HLA antigens a genetic model was suggested that differs somewhat from the currently accepted model. The new model is able to predict what would appear as linkage relations in the accepted model. Our methodology can provide alternate models to guide in typing cloned genes in terms of the HLA locus and alleles.     

Modifications of lymphocyte HL-A antigens as a consequence of therapy in patients with manic-depressive psychosis]

In 54 (= 46.96%) of 115 patients with maniacal-depressive psychosis a HLA modification could be identified. This modification turned out to be temporary and from a serological point of view it revealed a different character. In 29 cases a loss of HLA antigens could be observed, in 3 cases there was a decrease, in 14 cases a combination of both changes, twice a polyreactivity was observed and 6 times a change of the antigen HLA-A 2 in A 28 could be determined. These serological modifications appeared after therapy with lithium as well as with various antidepressive and neuroleptic medicaments. The connection between therapy and development of HLA modification could be ensured statistically. The modifications of HLA antigens A 10 and B 7 developed after administering neuroleptic medicaments, those of HLA antigens A 9, A 11, B 12, and B 13 after therapy with antidepressive medicaments. HLA antigens B 27 and B 40 showed a relative resistance towards therapy. The significance of these findings for the possibility of mistakes in HLA typing and from the standpoint of therapy efficiency in connection with the patient's HLA phaenotype is discussed.     

HLA compatibility and survival of 51 chromium-labeled allogeneic thrombocytes

In 37 patients with thrombocytopenia (mostly with ITP) the survival time of 51Cr-labeled allogeneic platelets was investigated. The HLA antigens were typed in donors and recipients and the presence of HLA cytotoxins and specific thrombocyte antibodies in sera of patients were examined. In 7 cases the identity of 2 HLA antigens, in 15 cases that of 1 HLA antigen and in 15 cases the HLA incompatibility between donor and patient were found. The survival of platelets did not depend on the degree of HLA compatibility, unless the HLA cytotoxins in sera of patients appeared. The HLA, as well the specific platelet antibodies brought about the shortened platelet survival to 1 day and less. The importance of these observations for platelet kinetics is discussed.     

Cytotoxic antiglobulin test--a sensitive method for HLA typing

By using of 1:1000 of diluted antiglobulin sera the cytotoxic antiglobulin test also covers HLA antigens in 20% of those cases which cannot be identified by normal microlymphocytotoxic tests. The percentage of not specifically faulty positive results is lower than 5%. The method can be used for typing HLA antigens in all those cases where a decreased expressiveness of HLA antigens can be expected as well as for determining weak HLA cytotoxins. The use of undiluted antiglobulin sera, however, leads to unspecific positive results in 1/4 of the cases. The reasons for this phenomenon are being investigated and discussed.     

The HLA system and its contribution to the genetics of rheumatic diseases

The results of the study of histocompatibility antigens at loci A, B and Dr in patients with RA and SLE, and their first degree relatives are presented. HLA antigens B12. B18, B27, Dr2 and Dr4 were associated with RA. The antigens HLA A11, B7, B35, Dr2 and Dr3 were associated with SLE. The influence of HLA antigens on formation of clinical picture of RA and SLE was determined. Evaluation of interallelic and interloci antigens interaction in a relative risk of disease suggests that, in some cases, there is a "superdominance" effect. Some combinations of HLA antigens at loci B and Dr increase the disease risk for RA and SLE. Analysis of test-marker linkage to genes predisposed to RA and SLE provides no direct confirmation of the hypothesis of their location on the short arm of the sixth chromosome between loci B and Dr, though this possibility cannot be completely excluded.     

Increased incidence of faecal Klebsiella pneumoniae in patients with HLA B7 CREG antigen and men with rheumatoid arthritis.

In a study of the carriage of faecal Klebsiella pneumoniae in 106 patients with rheumatoid arthritis the incidence of carriage was higher in men (28%) than women (14%) (p < 0.001) and klebsiellae were isolated on two or more occasions from a higher proportion of men than women (p < 0.002). The incidence of carriage was increased among patients with rheumatoid arthritis who had B7 cross-reacting (B7 CREG) antigens (32% v 13%--p < 0.001). Carriage of klebsiellae was not associated with clinical disease activity, raised erythrocyte sedimentation rate, drug treatment, or the presence of HLA Dw4 or DRw4 or both. Thus the carriage and prevalence of faecal Klebsiella pneumoniae appear to be partly determined by the sex and HLA state of the host.     

Nature of the distribution of HLA system antigens among the inhabitants of the Carpathian genogeographic zone of the Ukrainian SSR

Distribution of HLA system leukocytic (tissue) antigens among the population of Carpathian genogeographic zone and among Ukrainian population of the native inhabitants of this region was studied, for the first time. The data characterizing the distribution, gene set and relationships of HLA antigens in A, B and C loci were obtained. It will be possible to discuss the distribution peculiarities of HLA system leukocytic antigens among the population of Carpathian zone after the work in all genogeographic zones of the Ukrainian SSR is completed and and the maps are published.