Standardisation and quality assurance of lymphocyte proliferation assays for use in the assessment of immune function. European Concerted Action on Immunological and Virological Markers of HIV Disease Progression.

Lymphocyte proliferation is a widely used technique to assess immune competence. However, the technique is subject to a large degree of variation, some biological and some technical. In this study, the components of variation in whole blood proliferation assays were analysed over time, using both antibody and mitogenic stimulants. The levels of variation within individual samples, between individuals and between groups of individuals over time were examined. A method of transforming the data is proposed which reduces the coefficients of variation to an acceptable level, and which expresses individual results as a standardised count. This method overcomes the problem of different levels of absolute counts, it corrects for time sensitive errors and allows data from multiple laboratories to be pooled.

Association between HLA antigens and progression of HIV infection in Greek haemophiliacs.

The frequencies of HLA antigens in 33 HIV seronegative and in 88 HIV seropositive haemophiliacs, who have been followed for at least 6 years since seroconversion or first HIV positive test, were evaluated in relation to disease susceptibility and disease progression. A high frequency of HLA-A2 and -DR2 antigens and a low frequency of HLA-A9 were found to characterize HIV seropositive patients (p < 0.05). Progressors to symptomatic CDC stage IV had a higher frequency of HLA-A9 (p < 0.01) and DR3. Rapid decline of CD4+ T cells in these patients was associated with HLA-A9, -DR1 and DR3. Our data suggest that HLA antigens may contribute to susceptibility to HIV infection and disease progression in Greek haemophiliacs.

HLA-A,-B, and -DR antigens in relation to gold and D-penicillamine toxicity in Greek patients with RA.

Ninety-five rheumatoid arthritis patients treated with aurothiomalate and/or D-penicillamine have been studied for possible associations between HLA-A, -B, -DR antigens and various toxic reactions to the above drugs. HLA-DR3 and -DRw6 had a higher frequency in patients with toxic reactions (all types) than in patients without toxic reactions (28.5 per cent vs 13.0 per cent and 26.5 per cent vs 4.3 per cent, chi 2 = 2.6 and 7.2, respectively). HLA-B8 was found at a higher frequency in patients with proteinuria and other types of renal involvement (20.0 per cent vs 7.4 per cent in controls), whereas skin manifestations were mainly associated with the presence of HLA-DRw6. The lowest frequency of side-effects was seen in patients with HLA-DR1 and DR2 (10.2 per cent vs 28.3 per cent and 28.5 per cent vs 54.3 per cent, chi 2 = 3.9 and 5.5, respectively). In addition, seropositive patients possessing HLA-DR1, showed toxic reactions less frequently.

Serum immunoglobulin concentrations before and after splenectomy in patients with homozygous beta-thalassaemia.

Serum IgM, IgA, and IgG concentrations were measured in 19 patients suffering from blood-dependent homozygous beta-thalassaemia. The study was prospective and the same patients served as presplenectomy controls. IgG levels rose rapidly and continuously after splenectomy IgA levels also rose but not so sharply. IgM fell to low levelr pattern was found in the cross-sectional part of the study comprising 39 splenectomised and 51 non-splenectomised patients who were tested once.

Serum immunoglobulins in a rural and an urban population of Greece with special reference to immunoglobulin A.

The serum concentration of immunoglobulins G, A, and M was studied in 390 inhabitants of a rural community and in 204 residents of an urban area of Greece. It was found that serum IgA levels were significantly higher in the rural area where intestinal infections were more prevalent. No significant difference in serum IgG was found between the two groups. IgM was found to be lower among residents of the rural area. The present findings suggest a possible ecological association between increased IgA and chronic exposure to intestinal infection.

Carcinoembryonic antigen in thyroid disease.

Plasma carcinoembryonic antigen (CEA) levels were measured by the Z-Gel technique in 138 patients with benign thyroidopathies, 25 patients with thyroid cancer, and 141 normal persons. Levels were raised (above 5 ng/ml) in 2% of the normal subjects, in none of the patients with benign thyroidopathies, and in 20% of the patients with thyroid cancer. They were considerably raised in all cases of medullary carcinoma of the thyroid but they were also high in other histological types of thyroid cancer. Measurement of plasma CEA may be of value in the preoperative diagnosis and follow-up of patients with thyroid cancer.

Immune abnormalities in myelodysplastic syndromes.

The immune states of 52 patients with myelodysplastic syndromes classified according to the FAB criteria were studied. Serum electrophoresis and immunoelectrophoresis, direct Coombs test, and tests for organ and non-organ specific antibodies were performed. Twenty six patients had immunoglobulin abnormalities: six (11.5%) had monoclonal gammopathy; 17 (32.6%) had polyclonal increases in serum immunoglobulin; while in three (5.8%) immunoglobulin concentrations were decreased. The distribution of immunoglobulin abnormalities among the five myelodysplastic syndrome subtypes was fairly uniform. Results of direct Coombs test were negative in all cases. Organ specific antibodies were not detected in any of the patients tested, although two patients were found positive for antinuclear antibodies. The presence of immunoglobulin abnormalities indicates an involvement of the lymphoplasmatic system in myelodysplastic syndromes.

Some epidemiologic studies of HBSAg in Greece.

In an epidemiologic study in 17 villages from different areas of Greece, 2898 persons were examined in order to find possible relations between HBSAg prevalence, altitude and endemic goitre morbidity. A lower prevalence with a significant difference was found in areas with a high altitude as compared with those with a low one, in endemic goitre than non-endemic areas, and in low altitude endemic than in low altitude non-endemic areas. Goitrous subjects had a lower HBSAg prevalence than non-goitrous subjects, but the difference was of borderline significance. The results can probably be explained by the presence of an environmental factor associated with altitude acting together with a host factor predisposing to endemic goitre and favouring the immunity to HBV infection.

HLA antigens as predictors of disease progression in HIV-infected haemophilia patients (a 22 years' follow up).

Our objective was to assess the influence of genetic factors such as HLA classes I and II antigens and other clinical and laboratory variables on the progression of HIV disease in a cohort of 118 HIV infected haemophilic subjects of Greek origin who had been typed for HLA antigens and were followed up prospectively for 22 years since seroconversion. At the end of the follow up we compared two groups of patients: 22 patients who had a fast progression to AIDS (median 6 years since seroconversion) vs. 33 patients who remained asymptomatic in stage A2 for up to 22 years (median 15 years). The results showed that the two groups did not differ significantly in age at seroconversion or baseline CD4+ T cell count. However there was a difference in the frequencies of certain HLA antigens in the two groups. The fast progressors had a higher frequency of HLA-A28, B21 and DR3, which was statistically significant (P = 0.02, 0.04, 0.05, respectively) compared to the slow progressors. These findings based on classical HLA typing techniques confirm other published observations and support the effect of genetic background in the progression of HIV infection in haemophilics.

Problems related to treatment of beta-thalassaemia major.

New developments in the symptomatic treatment of beta-thalassaemia major are expected to improve the quality of life and survival of the patients. However, there are still many problems related to the clinical management of the patients due to the severity of the disease per se and the complications of blood transfusion and iron overload. Some of the problems related to the treatment of hypersplenism, post-transfusion complications, bone manifestations, hormonal deficiencies and haemosiderosis are reviewed in the light of recent investigations.

alpha-Chain disease causing kaliopenic nephropathy and fatal intestinal perforations.

A case of alpha-chain disease (alpha-CD) is described presenting as a malabsorption syndrome complicated by severe kalipenic nephropathy. Antibiotics and cyclophosphamide were effective in controlling the malabsorption and thr renal dysfunction but did not affect the basic pathological lesion. Eventually the disease became generalized, affected lymph nodes, liver and bone marrow and caused multiple intestinal perforations. Detailed histological studies failed to demonstrate the development of reticulum-cell sarcoma as a terminal complication of the disease and are suggestive of a single malignant plasmacytic cell process.

Disturbance of cell-mediated immunity in patients with carcinoma of colon and rectum.

The cellular immune mechanisms of patients with adenocarcinoma of colon or rectum were evaluated by studying the lymphocyte response to PHA stimulation. Our results indicate that the serum of cancer patients causes a decreased blastic transformation and H(3) thymidine uptake of the lymphocytes of patients as well as of normal controls. A defect of the lymphocytes unrelated to serum factors was also present in some cancer patients. However, no relationship was found between the degree of transformation and the presence of metastases in the lymph nodes.

Malabsorption associated with nonmalignant immunoproliferative small intestinal disease.

Two cases of nonmalignant immunoproliferative small intestinal disease (IPSID) presenting with severe malabsorption are described. The first patient had a lymphocytic infiltrate of the lamina propria and lymphoid hyperplasia of the mesenteric lymph nodes and responded to oral tetracycline. The second patient had a polyclonal plasmacytic infiltration of the lamina propria and of the mesenteric nodes and responded only to cytotoxic treatment with cyclophosphamide. These cases represent examples of non-alpha-chain disease benign IPSID.

Mycosis fungoides: evaluation of immunohistochemical criteria for the early diagnosis of the disease and differentiation between stages.

Lesional skin specimens from twenty-eight patients with mycosis fungoides were studied by evaluating immunohistochemical criteria, primarily with monoclonal antibodies. It was demonstrated that significant differences exist between the control and the premycotic-stage group in regard to the monoclonal antibodies BE1, BE2, and OKT9. The detection of specific antigenic determinants on the surface of cell populations early in the course of the disease seems to be of considerable value for the early diagnosis of the disease. Statistically significant differences were found between the premycotic stage and the plaque stage in regard to T lymphocytes, macrophages, OKT6+, OKT4+, OKT8+, and BE2+ cells in the dermal infiltrate. Significant differences were also shown between the plaque and tumorous groups, concerning macrophages, T cells, and OKT9+ cells in the dermis, as well as epidermal dendritic cells. Differences between stages may supplement histologic data for the follow-up of the disease with or without treatment.

Cutaneous delayed hypersensitivity in Crohn's disease and ulcerative colitis. Application of multi-test.

In this study the Multi-Test was applied in 48 patients with inflammatory bowel disease and in 25 normal controls. A significant difference between normal controls and patients with Crohn's disease but not between normal controls and patients with ulcerative colitis was found with regard to anergic status, frequency of positive skin reactions, and size of skin infiltration. The authors conclude that in patients with Crohn's disease a defect exists in the cellular immunity.