Valeria Stenszky

Immunogenetic and immunologic studies of differentiated thyroid cancer

The authors have studied in detail human leukocyte antigen (HLA) association in 87 Hungarian patients with thyroid epithelial carcinoma. The authors also examined in a small group of patients, five parameters of cell‐mediated immunity and related them to HLA as well as to lymphocytic infiltration of the tumor/ normal tissue interface. HLA‐DR1 was significantly associated with thyroid carcinoma; the strongest association was in patients with follicular histologic features and DRI homozygotes were not at greater risk for thyroid cancer. The HLA‐DR3 was nonsignificantly increased in patients with papillary or mixed histologic features. The HLA‐DR1, 3 heterozygotes were highly associated with follicular carcinoma, carried no risk for papillary carcinoma, and an intermediate risk for tumors with mixed histologic features. Because of the small proportion of DR1, 3 heterozygotes in the follicular and mixed histologic group, its predictive value at the population level was low. Better predictive potential was shown for the phenotype DR1 and/or DR3. Neither metastatic disease nor age at diagnosis (<45 years) could be related to HLA phenotypes. Patients in all histologic variants showed some measure of cell‐mediated immunity compared to controls. Patients with papillary carcinoma showed an overall better response than those with tumors with follicular or mixed histology. The HLA‐DR could not be related to cell‐mediated immune response. Patients with papillary carcinoma with a good cell‐mediated immune response occurred with much lower infiltration of the tumor boundary with lymphocyte whereas the follicular carcinoma less cell‐mediated immunity was associated with dense lymphocytic infiltration, suggesting the biological relevance of lymphocytic infiltration may be different for the two histologic variants.

Cytotoxic endothelial cell antibodies in mixed connective tissue disease

We examined the presence of anti-endothelial cell antibodies in the sera of 44 patients with mixed connective tissue disease (MCTD). Warm antibodies against endothelial cells were found in 45.4% of patients; the presence of these antibodies was positively correlated with anti-monocyte antibodies (P less than 0.01) but not with anti-lymphocytic antibodies. Strong correlations were found between the presence of these antibodies and abnormalities of pulmonary ventilatory capacity, neurophysiologic and myocardial function. Anti-endothelial antibodies were related to the high rate of spontaneous abortion noted in female MCTD patients. The identification of the antigen identified by MCTD sera in endothelial cells would help in understanding disease manifestations.

HLA-DR1 is associated with vitiligo

In Eastern Hungary, vitiligo is found to be associated with HLA-DR1. When other autoimmune disorders are also present, DR3 is also increased.

The relation of susceptibility to and biologic behavior of thyroid epithelial cell cancer to HLA‐DR1

Fifty‐two patients with thyroid epithelial cell cancer were studied for evidence of association with human leukocyte antigens (HLA). Twenty‐eight patients (53.8%) and 19.4% of 160 controls were HLA‐DR1‐positive, conferring a relative risk of 4.85 (x2 = 21.3, P < 0.0001). HLA‐DR1 was increased in all histologic types of thyroid cancer. Interestingly 10 of 12 patients with metastatic disease were DR1‐positive compared to 18 of 41 patients without metastases (relative risk = 6.1, x2 = 4.7, P < 0.05). This study suggests that major histocompatibility complex‐linked gene(s) determine susceptibility to and the biologic behavior of thyroid cancer. Cancer 58:52–54, 1986.

B lymphocyte subsets in Hashimoto's thyroiditis

Two B lymphocyte subsets are identified on the basis of possession or lack of a surface molecule, CD5. The CD5+ B lymphocytes synthesize autoantibodies and in the process rearrange proximal variables of immunoglobulin genes. We have here studied the proportion and absolute counts of CD5+ B lymphocytes in the peripheral blood of 31 patients with Hashimotos thyroiditis and related the findings to their HLA phenotypes and clinical features. Although the percentage and absolute number of surface immunoglobulin-positive (B) lymphocytes was comparable in patients to those in twenty controls, % CD5+ was significantly higher in the patient group (38.1 +/- 11.6 [+/- S.D.] vs. 27.9 +/- 10.1, p = 0.009). The absolute CD5+ cells (microliters) were also higher in patients with Hashimotos thyroiditis (77.90 +/- 37.50 vs. 55.1 +/- 29.8, p = 0.020). The proportion of CD5+ cells was even higher in HLA-DR3 positive patients (43.1% +/- 7.2, n = 13) compared to six DR3+ controls (26.17% +/- 9.7, p = 0.0005). The difference between DR3- patients and controls was not significant (28.6% +/- 10.5 vs. 34.4% +/- 13.0). As the CD5 molecule may be induced on activated B lymphocytes, this study suggests that Hashimotos thyroiditis is associated with an increase of activated B lymphocytes engaged in autoantibody synthesis. This defect is particularly obvious in DR3+ patients.

HLA Control of Thyroglobulin-Induced Blast-Transformation in Graves’ Disease

We studied 80 patients with Graves’ disease for lymphocyte transformation in response to thyroglobulin. HLA-DR3 patients showed significantly greater response than DR.Vnegative patients.

Familial leukemia: Ph1 positive acute lymphoid leukemia of a mother and her infant

SummaryThe authors report the case of a mother and her infant who both suffered from acute lymphoid leukemia (ALL). Both leukemic processes proved to be Ph1 positive and of “0” cell character. In addition to the clinical and hematological findings the results of HLA antigen determination and cytogenetic studies are presented.