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Biomedical subjects

H K Machulla

Publications and source records attributed to H K Machulla.

11 recordsLinked to original sources
PubMed2001

Association of chronic lymphocytic leukemia with specific alleles of the HLA-DR4:DR53:DQ8 haplotype in German patients.

The etiology of chronic lymphocytic leukemia (CLL) remains unknown, though a genetic susceptibility has been suggested. Results of complete DNA typing of HLA alleles in CLL patients are lacking. We compared HLA class I and class II frequencies in 101 German CLL patients and 157 healthy German controls as determined by PCR-SSP/SSO DNA analysis and serologic typing. The most striking difference was the increased frequency of HLA-DRB4*0103 [relative risk (RR) = 2.74, p < 0.0025] among patients. The presence of alleles HLA-DRB1*0401, HLA-DQB1*0302 and HLA-DPB1*0301 as well as of homozygosity for HLA-DQB1 was also associated with a higher risk for CLL, though none of these differences remained significant after correction for multiple comparisons. No association was found for any HLA class I allele. Haplotype analysis revealed a CLL-specific linkage disequilibrium for HLA-DRB1*0401:DRB4*0103 and HLA-DRB4*0103:DQB1*0302. Our results suggest that CLL could be associated with distinct class II alleles of the Caucasian haplotype HLA-DR4:DR53:DQ8, which has also been related to a susceptibility for several auto-immune diseases. The positive, though weak, association of CLL with HLA-DPB1*0301 might represent an independent susceptibility factor since no linkage disequilibrium existed with any of the other CLL-associated alleles. None of the previously reported associations with HLA class I antigens was confirmed. Our results suggest that factors within or close to the human MHC class II region confer susceptibility to CLL.

Alleles↗
PubMed2001

Brain glioma and human leukocyte antigens (HLA)--is there an association.

Expression of human leukocyte antigens (HLA) is important for the immune response against infectious agents and malignant cells. Association of single HLA antigens or HLA haplotypes with disease has been investigated previously, and positive correlations between HLA and some cancers, such as cervical or nasopharyngeal carcinomas have been reported. In the present study, HLA antigen frequencies of 65 adult Caucasian patients with low-grade, anaplastic, or malignant astrocytic glioma (WHO grades II-IV) were compared with 157 racially similar, asymptomatic control individuals. Both standard serologic and PCR techniques for HLA typing were employed for all patients and controls. Our results suggest a positive association between single HLA antigens and presence of symptomatic cerebral glioma. Compared with the control population, patients positive for HLA-A*25 had a 3.0-fold increased risk of glioma (p = 0.04), patients positive for HLA-B*27, a 2.7-fold risk (p = 0.03), and patients positive for HLA-DRB1*15, a 2.2-fold risk (p = 0.03), whereas HLA-DRB1*07 was associated with a 0.4-fold decreased risk of glioma (p = 0.02). Occurrence rate of some HLA antigen combinations and estimated haplotypes was also different in glioma patients. Thus, HLA-DRB1*15:DRB5*(51) occurrence in combination with HLA-DRB1*11 was associated with a 13.4-fold increased risk of glioma (p = 0.001), and the incidence of HLA-Cw*6:DRB1*07 with a 0.2-fold decreased risk of glioma (p = 0.03). In conclusion, single HLA antigens and their combinations and estimated haplotypes are possibly significantly more or less frequent in persons developing symptomatic cerebral glioma during their adult life, compared with asymptomatic individuals.

Adult↗
PubMed1999

Unravelling an HLA-DR association in childhood acute lymphoblastic leukemia.

Genetic and environmental factors play an interactive role in the development of childhood acute lymphoblastic leukemia (ALL). Since the demonstration of a major histocompatibility complex (MHC) influence on mouse leukemia in 1964, an HLA association has been considered as a possible genetic risk factor. Despite extensive efforts, however, no strong evidence comparable to the H-2(k) influence on mouse leukemia has been shown. The number of negative serological studies resulted in a loss of interest and consequently, no molecular HLA-DR association study has been published to date. We reconsidered the HLA-DR association in childhood ALL in 114 patients from a single center and 325 local newborn controls by polymerase chain reaction (PCR) analysis of the HLA-DRB1/3/4/5 loci. With conventional analysis, there was a moderate allelic association with the most common allele in the HLA-DR53 group, HLA-DRB1*04, in the whole group that was stronger in males (P =.0005, odds ratio = 2.9). When the other expressed HLA-DRB loci were examined, homozygosity for HLA-DRB4*01, encoding the HLA-DR53 specificity, was increased in patients (21.1% v 8.3%; odds ratio = 2.9, P =.0005). Consideration of gender showed that all of these associations were reflections of a male-specific increase in homozygosity for HLA-DRB4*01 (32.8% v 4. 0%; odds ratio = 11.7, 95% confidence interval [CI] = 4.9 to 28.0; P = 3 x 10(-8)). This highly significant result provided the long-suspected evidence for the HLA-DR influence on the development of childhood ALL while confirming the recessive nature of the MHC influence on human leukemogenesis as in experimental models. The cross-reactivity between HLA-DR53 and H-2Ek, extensive mimicry of the immunodominant epitope of HLA-DR53 by several carcinogenic viruses, and the extra amount of DNA in the vicinity of the HLA-DRB4 gene argue for the case that HLA-DRB4*01 may be one of the genetic risk factors for childhood ALL.

Abortion, Habitual↗
PubMed1999

Early-onset periodontitis in a patient with Ehlers-Danlos syndrome type III.

This case history describes the course of disease in a 17-year-old boy with Ehlers-Danlos syndrome type III and early-onset periodontitis. Flow cytometric tests showed a reduced cell count in the specific immune system. Immunoglobulin concentrations in saliva and serum were within normal limits. Infection with T-lymphotropic viruses was excluded. The phagocytic capacity of the peripheral blood polymorphonuclear leukocytes was unimpaired. The anaerobic infection present in the early-onset periodontitis was treated with systemic antibiotic therapy and closed curettage. Following 14 days of this treatment, signs of acute inflammation subsided, and 18 months after therapy ended, a slight gain in clinical attachment was found, and bone growth was visible via radiology. However, a continuing lack of adequate oral hygiene represents a risk to the success of therapy in the long term.

Adolescent↗
PubMed1997

High-resolution DNA typing in immunoglobulin A deficiency confirms a positive association with DRB1*0301, DQB1*02 haplotypes.

Selective immunoglobulin A (IgA) deficiency, the most common form of primary immunodeficiency, is related to the HLA genes. Previous studies demonstrated associations with particular HLA-DR-DQ haplotypes and a neutral amino acid at position 57 of the DQbeta chain was implicated in the susceptibility to selective IgA deficiency. In this study we reanalyzed the reported findings by high-resolution DNA typing of the loci DRB1, DQB1 and DQA1. We compared the typing results of 74 IgA-deficient individuals, detected by screening of blood donors, with those taken from 111 healthy controls. Results confirmed a strong positive association with DRB1*0301, DQB1*02 and a negative association with DRB1*1501, DQB1*0602. Considering the molecular interactions between HLA class II alleles and the peptides bound we conclude that the amino acid at position 57 of the DQbeta chain may contribute to the susceptibility to selective IgA deficiency, but not determine it. An extended statistical analysis strengthened the hypothesis that selective IgA deficiency might be communicated by the distinct haplotype DRB1*0301, DQB1*02.

DNA↗
PubMed1996

Influence of the major histocompatibility complex on age at onset of chronic lymphoid leukaemia.

The major histocompatibility complex is one of the interactive factors in the multifactorial model of carcinogenesis. Its main influence in experimental models is on the age at onset of malignancies. We have previously shown a similar effect of homozygosity for HLA-DR53 in CML. In the present study, we investigated 79 patients with CLL and 329 local controls from Germany. In addition to full serotyping, all patients and 116 of controls were also typed by HLA-DRB PCR analysis. The homozygosity rates for DR53 in patients under and over the median age (60 years) were 18.6% and 2.9%, respectively (p = 0.03). Eight of the 9 homozygous patients were under the median age. The sex ratio in the DR53 homozygous group was reversed in favour of females. The homozygosity rates for DR53 were different in the overall groups of patients and controls, yielding a relative risk (RR) of 2.4 (p = 0.03). This association was stronger in the early-onset group compared to age-matched controls (RR = 4.4; p = 0.008) and for females with an early onset compared to age- and sex-matched controls (RR = 17.9; p = 0.0008). The simultaneous occurrence of the alleles of the haplotype A2B62DR4 showed a strong association with CLL (RR = 4.1; p = 0.002). This was probably the reason behind the association with HLA-DRB1*0401 (RR = 2.4; p = 0.009). Compared to the accelerating effect of HLA-DR53, HLA-DR52 showed a significant delaying effect on the onset of CLL. These findings confirmed the influence of the HLA complex on the development of another leukaemia.

Adult↗
PubMed1994

[HLA and selective IgA deficiency].

A selective deficiency of IgA is developed significantly (p < 0.05) more frequently by HLA-A2-negative than by HLA-A2-positive healthy persons. The frequent combination of A1/A3 is absent. The incidence of HLA-B8-positive persons is increased (p < 0.01). A selective disadvantage is discussed.

Gene Frequency↗
PubMed1979

[Studies of the antibody heterogeneity in carp (Cyprinus carpio L.). I. Electrophoretic and isoelectric spectra of anti-DNP-antibodies].

Carp IgM as well as carp anti-DNP-antibodies migrate electrophoretically very well as a diffuse band into polyacrylamide gel of large pore size. The isoelectric spectra of the carp anti-DNP-antibodies are heterogeneous and show bands in the pI-range of 4.0 to 6.4. The activity of focused anti-DNP-antibodies could be demonstrated in the pI range between 5.4 to 6.4 even in high antibody dilutions. The investigated structural heterogeneity of the anti-DNP-antibodies of carp is a further proof for the phylogenetically early onset of a large antibody heterogeneity of lower vertebrates.

Animals↗