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L Kozma

Publications and source records attributed to L Kozma.

At least 37 records · Page 2Linked to original sources
PubMed1986

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 (chi 2 = 21.3, P less than 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, chi 2 = 4.7, P less than 0.05). This study suggests that major histocompatibility complex-linked gene(s) determine susceptibility to and the biologic behavior of thyroid cancer.

Antigens, Neoplasm↗
PubMed1986

Interaction of IgG heavy-chain allotypes (Gm) and HLA in conferring susceptibility to thyroid carcinoma.

We have recently reported an increase in HLA-DR1 in 52 patients with thyroid epithelial cancer from Eastern Hungary (Juhasz et al., 1986). We have now investigated the association of IgG heavy chain markers (Gm) in 50 patients with this disease and explored possible interaction between Gm and HLA in modifying the risk for thyroid cancer. No Gm phenotype showed significant increases in the patients compared to 168 local controls. When both Gm and HLA, however, were considered, a marked heterogeneity in risk was noted. The odds ratio for DR1+fb+ homozygotes was 37.5, for DR1+fb- individuals 6.0 and for DR1-fb+ individuals 2.6 (DR1-fb- = 1.0). Thus Gm and HLA interact to enhance greatly the risk of thyroid cancer.

Disease Susceptibility↗
PubMed1986

Genetic factors in Graves' ophthalmopathy.

We investigated the distribution of HLA and immunoglobulin G heavy chain markers (Gm) in 117 patients with Graves' disease, 62 with ophthalmopathy and 55 without. With Graves' disease per se, there is a closer association with HLA-DR3 than with B8. The opposite was true for Graves' patients with ophthalmopathy (odds ratio for ophthalmopathy associated with B8 was 12.4 and with DR3 was 7.7, both with P less than 0.0005). HLA-DR7 interacts with B8 in modifying the risk for eye disease; using the phenotype B8- DR7- as reference, the odds ratios were 16.7 for B8+ DR7+, 8.7 for B8+ DR7- and 0.26 for B8- DR7+. Thus, DR7 enhanced the risk for ophthalmopathy in the presence of B8+ but had a protective influence in its absence. Although Gm showed no association with eye disease, it modified the risk for ophthalmopathy associated with HLA-B8; the odds ratios were 20.9 for B8+ Gmfb homozygozity (fb+), 15.3 for B8+ fb- and 1.7 for B8- fb+ (B8- fb- = 1.00). We conclude that the genetic factors contributing to Graves' ophthalmopathy are different from those related to liability for Graves' hyperthyroidism.

Autoimmune Diseases↗
PubMed1986

Interplay of immunoglobulin G heavy chain markers (Gm) and HLA in predisposing to systemic lupus nephritis.

We have studied the distribution of IgG heavy chain markers (Gm) among 90 Hungarian patients with systemic lupus erythematosus (SLE) (55 of whom were also typed for HLA). This study confirms previously described increases in HLA-B8 and DR3 in this condition. No difference in the distribution of Gm phenotypes was found between patients and 168 controls from the same geographical area. HLA-B8/Gm homozygous individuals were, however, at greater risk for SLE (relative risk = 5.13) compared to B8 + Gm heterozygotes or B8- individuals, irrespective of Gm phenotype. When patients with renal manifestation (n = 40) were compared to those without, the Gm phenotype 3; 5, 13 was found to be significantly increased (chi 2 = 10.36, P less than 0.0001, relative risk (RR) = 4.69). HLA and Gm increased additively the risk for renal manifestations in that for those patients who were both Gm3;5,13+ and HLA-B8+, PR was 110, while it was 21.2 for Gm3;5, 13-/B8+, 7.9 for Gm3;5, 13+/B8- and 1.0 for Gm3;5, 13-/B8- patients. The study suggests that combined HLA and Gm typing can be used to identify SLE patients at high risk for manifesting renal abnormalities.

Genetic Markers↗
PubMed1986

Heterogeneity of systemic lupus erythematosus elucidated by cluster analysis. The influence of HLA.

For 75 patients with systemic lupus erythematosus (SLE), 39 laboratory and clinical characteristics, including HLA-A, B, C and DR typing, were analysed using a cluster analysis technique. Three groups were identified. Group I (46 patients) was characterized by infrequently severe disease, good response to therapy and infrequent multisystem involvement. Group II (24 patients) was characterized by a severe course of disease (although the tendency to remit after therapy was not unusual), and frequently, renal involvement and pericarditis. Group III (5 patients) was characterized by more severe renal disease. Of the 75 patients studied, 38.7% possessed HLA-DR3, compared to 17.4% of controls. Group I patients did not differ from controls but 80% of Group II patients and 4/5 Group III patients had DR3. Cluster analysis identifies subsets of SLE patients who show marked differences in disease course and severity, correlated with possession of the HLA B8, DR3 phenotype.

HLA Antigens↗
PubMed1986

Heterogeneity by cluster analysis techniques of Graves' patients typed for HLA DR and IgG heavy chain markers.

In a previous study we were able to separate, using cluster analysis, 196 patients with Graves' disease evaluated for a large number of clinical and laboratory characteristics, including HLA-A and HLA-B typing into one subset with recurring disease and a high prevalence of ophthalmopathy and another subset with mild disease and little ophthalmopathy. Prevalence of HLA-B8 was much higher in the first as compared to the second group. The present study was undertaken in 117 new patients with Graves' disease, typed for HLA-A, HLA-B, HLA-C and DR antigens and IgG heavy chain markers, to determine whether these characteristics could be used to segregate patients into clinically relevant subsets. There was a greater proportion of Gm fb homozygotes among patients than among controls (chi2 = 4.71, p less than 0.05) as well as individuals with HLA-B8 and DR3, previously documented for this disease. Two patient clusters were identified. In one (C1), there is a high incidence of exophthalmos, recurrence of hyperthyroidism after drug treatment, high titres of anti-thyroglobulin antibody, and an association with other autoimmune (including thyroid) diseases, a tendency for the disease to be familial and the presence of larger goitres. The incidence of HLA-B8 was greater in C1, while HLA-B12 was more frequent in the mild cluster, C2. HLA-DR3 was found to be associated with patients in the severe cluster and HLA-DR2 with patients in the mild cluster.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1986

The role of HLA antigens in the manifestation and course of Graves' disease.

Graves' disease is associated with HLA-DR3 in Caucasoids. We have now demonstrated, on the basis of disease-associated MHC haplotypes (A1, Cw3, B8, DR3 and fragments thereof) from 38 families in which more than one member had Graves' disease compared with MHC haplotypes from 56 healthy families, that the risk was highest with the DR locus (relative risk for A1, B8, DR3 = 2.3, for B8, DR3 = 5.3, and for DR3 = 6.8). We further used the sib-pair method to explore linkage of Graves' disease liability to the MHC in 67 affected sib-pairs. The data were consistent with an MHC-linked recessive gene with a frequency of 0.2 to 0.3 and a penetrance of 7.2%; the data, however, accommodated penetrance of up to 16.3%. A recessive model was also consistent with the HLA-B8 genotype distribution in 286 unrelated patients. As the effect of the marker alleles on the course of the disease had been debated several times, we applied a cluster analysis method using 49 clinical and laboratory characteristics, including the HLA-A and HLA-B antigens of 196 patients. Three groups were identified, corresponding to patients with mild disease, Hashitoxicosis and severe (relapsing) disease. The prevalence of HLA-B8 was 8.9%, 21% and 87%, respectively (compared to 18.8% in 380 controls). This suggests the existence of an underlying continuum of genetic liability, apparently related to that for Graves' disease severity, associated with the MHC and mediated through immunoregulatory disturbances.

Adolescent↗
PubMed1985

The genetics of Graves' disease: HLA and disease susceptibility.

To relate genetic variation in Graves' disease (GD) susceptibility to polymorphism at MHC loci, clinical and family studies were undertaken in eastern Hungary. Among 1980 relatives of 534 index patients, 2.9% of siblings, 2.7% of offspring, and 3.0% of parents had GD. HLA haplotype combinations in affected sibling pairs were determined in the present data and combined with data in the literature (12 sibling pairs from Farid 1981, 12 from Chan et al. 1980, and 15 from Sasazuki et al. 1983); 43, 23, and 1 affected sibling pairs shared, respectively, 2, 1, and 0 HLA haplotypes. This distribution is inconsistent with simple dominant inheritance, but is consistent with simple recessive inheritance of HLA-related susceptibility over a range of gene frequencies (0.2-0.4). A frequency of 0.3 gives the best fit and is consistent with penetrance of 7.1% for the recessive susceptibility genotype; the data, however, can accommodate penetrance values up to 16%. The distribution of HLA haplotypes in 33 families related disease susceptibility more strongly to DR than to other loci. The distribution of HLA-B8 genotypes in 256 patients was in close agreement with Hardy-Weinberg equilibrium proportions, also favoring recessive inheritance of MHC-related susceptibility. The probability that an individual will be affected with GD can be predicted, based on sex, HLA genotype, and family history. For example, 14.9% of DR3-positive women with an affected first degree relative are likely to be affected. These predictions can be tested as family data accumulate.

Adolescent↗
PubMed1985

The association of IgG heavy-chain allotypes (Gm) with Graves' disease in Hungary.

In an Eastern Hungarian population of patients, we sought to confirm an association with IgG heavy-chain allotypes (Gm) with Graves' disease. We found an increase in the phenotype fb (chi 2(1) = 4.7, p less than 0.05) among the patient group compared to controls. The influence of Ig-linked genes to Graves' disease susceptibility is, thus, dose-dependent. We found no interaction between fb homozygosity and HLA-DR3 positivity in Graves' disease susceptibility.

Disease Susceptibility↗
PubMed1984

Specific suppressor T cell function in a patient with Graves' disease and her healthy identical twin.

Immunoregulatory defects have been suggested in autoimmune disorders including Graves' disease. The finding that Concanavalin A-induced suppressor T cell function was sub-optimal in Graves' disease has been disputed; a restricted defect in TSH-receptor antigen-specific suppressor cells has instead been proposed by Okita et al. (1980). To explore this further, we studied both specific and non-specific suppressor cell function in a pair of HLA identical twins, one of whom had Graves' disease. By contrast to the euthyroid healthy twin and 10 healthy controls (612 cpm/10(6) cells) the patient's mononuclear cells (MNCs) incorporated more (3H)-thymidine (7365 cpm/10(6) cells) in response to thyroid membrane antigen (TMA). Removal of glass-adherent cells before addition of antigen increased (3H)-uptake by cells from the healthy twin to 1808 cpm but reduced those from the Graves' twin to 3411 cpm. The influence of MNCs cultured with Con A or TMA for 24 h upon (3H)-thymidine uptake by 2 X 10(6) indicator cells triggered by Con A for 72 h or TMA for 96 h was taken as a measure of non-specific and specific suppressor cell function respectively. Both Con A and TMA induced suppressor cells were reduced, the latter to a more marked degree, in the patient compared to the healthy twin; mixing of MNCs from patient and healthy twin in a 1:1 ratio improved the patient suppressor cell function. When the patient's MNCs triggered for 24 h with Con A were mixed in a 1:1 ratio with her fresh MNCs and TMA, less blast transformation was found compared to an equal number of fresh cells (3H-thymidine uptake 3250 vs 7365 cpm/10(6). Similarly, preincubated cells from the healthy twin had greater suppressive effect (1820 cpm/10(6) cells). We conclude that (1) the HLA identical healthy twin has TMA autoreactive lymphocytes regulated by adherent regulatory cells; (2) the increased ratio of helper/suppressor cells in the adherent cell population in the patient leads to a decrease of (3H) incorporation upon their removal; (3) in the patient, the specific suppressor cell defect is more severe than the non-specific defect; (4) lack of specific TMA induced triggering may be the critical immunoregulatory defect in Graves' disease.

Adult↗
PubMed1983

Identification of subsets of patients with Graves' disease by cluster analysis.

We have applied cluster analysis methods to forty-nine laboratory and clinical characteristics (including 26 HLA-A, B antigens) observed in 196 Graves' disease patients. Three subgroups could be identified: group I (seventy-nine patients) had small goitres, low indices of autoimmunity and a tendency to remission with medical treatment; group IIa (twenty-nine patients) had clinical and laboratory features of 'Hashitoxicosis'; Group IIb (eighty-four patients) had a high incidence of ophthalmopathy, familial aggregation, marked evidence of autoaggression and a tendency to relapsing hyperthyroidism. The prevalence of HLA-B8 was 8.9% in group I, 20.7% in group IIa and 86.9% in group IIb. This study demonstrates that Graves' disease can be subdivided using cluster analysis into clinically relevant subgroups which are further distinguished by their correlation with HLA-B8. Possible immunological bases for these observed patterns are discussed.

Adolescent↗
PubMed1983

HLA-DR associations with Graves' disease in eastern Hungary.

We have typed 196 patients with Graves' disease from eastern Hungary (an iodine-deficient region) for HLA-A, -B, and -C antigens and 80 of the same patients for HLA-DR antigens. Our data confirm the previously described association of HLA-B8 and DR3 with Graves' disease, particularly in patients with ophthalmopathy. We also describe several new findings: an increase in the prevalence of HLA-BW35, particularly in combination with B8, among patients with ophthalmopathy and a slight increase in the prevalence of B8, DR7 among patients with ophthalmopathy. These results support the concept that MHC-linked susceptibility to Graves' disease is dose-dependent. Our results do not confirm a report suggesting that the prevalence of HLA-DR5 is increased among patients without ophthalmopathy in iodine-deficient areas: we found that the prevalence of HLA-DR5 was slightly decreased among patients with Graves' disease, with and without ophthalmopathy, in comparison with controls.

Eye Diseases↗
PubMed1981

Clinical relevance of cytotoxic antibodies occurring in pregnancy.

Cytotoxic antibodies were studied in 809 pregnant women's sera. Two kinds of antibody population: HLA-A, B, C and Ia-like, were detected and a correlation was established between their presence and some clinical conditions, such as preterm delivery, spontaneous abortion, pre-eclampsia, neonatal hyperbilirubinaemia and congenital anomalies. An opposite effect of HLA-A, B, C and Ia-like antibodies was observed as far as the first three parameters are concerned. On the basis of these investigations a protective role of Ia-like antibodies for the newborn can be implied.

Abortion, Incomplete↗
PubMed1980

[Thoracic and abdominal injuries caused by safety belts (author's transl)].

Based on experiences over half a year authors found that the introduction of safety belts, beside obvious advantages, resulted in new types of injuries. They describe own experiences and draw attention to heart contusions joining thoracic fractures, and to possible thoraco-abdominal organ injuries with characteristic symptom free or delayed appearance, caused by blount trauma.

Abdominal Injuries↗
PubMed1979

HLA-antigens and some autoimmune features of juvenile diabetes mellitus.

A group of 67 juvenile insulin dependent diabetic patients and their 167 healthy first degree blood relatives were HLA-typed. In the patients the frequency of HLA-A9 and B8 antigens was significantly increased as compared to healthy controls, while in the family members only the presence of HLA-B8 was significantly increased. All diabetics carrying HLA-B8 antigen had frequently higher 125I-insulin-antibody complex levels than those lacking the antigen. Prevalence of some autoantibodies to human thyroglobulin, microsomal thyroid and antigastric mucosa antigen were investigated and compared to healthy controls. Increased antibody titres were more frequent in diabetics and their blood relatives than in the healthy controls, and more frequent in those carrying the HLA-B8 antigen than in those lacking it.

Adolescent↗