HLA class II associations with rheumatic heart disease among clinically homogeneous patients in children in Latvia

Genetic control of immune reactions has a major role in the development of rheumatic heart disease (RHD) and differs between patients with rheumatic fever (RF). Some authors think the risk of acquiring RHD is associated with the HLA class II DR and DQ loci, but other views exist, due to the various HLA-typing methods and ways of grouping cases. Our goal was to determine the relations between HLA class II alleles and risk of or protection from RF in patients with relatively homogeneous clinical manifestations. A total of 70 RF patients under the age of 18 years were surveyed in Latvia. HLA genotyping of DRB1*01 to DRB1*18 and DQB1*0201-202, *0301-305, *0401-402, *0501-504, and *0601-608 was performed using polymerase chain reaction sequence-specific primers. Data for a control group of 100 healthy individuals typed for HLA by the same method were available from the databank of the Immunology Institute of Latvia. Of the RF patients, 47 had RHD and 8 had Sydenham's chorea. We concluded that HLA class II DRB1*07-DQB1*0401-2 and DRB1*07-DQB1*0302 could be the risk alleles and HLA class II DRB1*06 and DQB1*0602-8, the protective ones. Patients with mitral valve regurgitation more often had DRB1*07 and DQB1*0401-2, and patients with multivalvular lesions more often had DRB1*07 and DQB1*0302. In Sydenham's chorea patients, the DQB1*0401-2 allele was more frequent. Genotyping control showed a high risk of RF and RHD in patients with DRB1*01-DQB1*0301-DRB1*07-DQB1*0302 and DRB1*15-DQB1*0302-DRB1*07-DQB1*0303

HLA class II DR and DQ genotypes and haplotypes associated with rheumatic fever among a clinically homogeneous patient population of Latvian children

Copyright: Copyright 2008 Elsevier B.V., All rights reserved.The HLA system is being paid more and more attention because it is very significant in polymorphous immunological reactions. Several studies have suggested that genetic susceptibility to rheumatic fever (RF) and rheumatic heart disease (RHD) is linked to HLA class II alleles. We hypothesized that HLA class II associations within RHD may be more consistent if analysed amongst patients with a relatively homogeneous clinical outcome. A total of 70 RF patients under the age of 18 years were surveyed and analysed in Latvia. HLA genotyping of DQA1, DQB1 and DRB1 was performed using PCR with amplification with sequence-specific primers. We also used results from a previous study of DQB1 and DRB1 genotyping. In the RF patients, HLA class II DQA1*0401 was found more frequently compared to DQA1*0102. In the RF homogeneous patient groups, DQA1*0402 has the highest odds ratio. This is also the case in the multivalvular lesion (MVL) group, together with DQA1*0501 and DQA1*0301. In the chorea minor patients, DQA1*0201 was often found. Significant HLA DQA1 protective genotypes were not detected, although DQA1 genotypes *0103/ *0201 and *0301/*0501 were found significantly and frequently. In the distribution of HLA DRB1/DQA1 genotypes, *07/ *0201 and *01/*0501 were frequently detected; these also occurred significantly often in the MVL group. The genotype *07/*0201 was frequently found in Sydenhamn's chorea patients that had also acquired RHD, but DRB1*04/DQA1*0401 was often apparent in RF patients without RHD. In the distribution of HLA DQA1/DQB1 genotypes, both in RF patients and in the homogeneous patient groups, the least frequent were *0102/*0602-8. The genotype DQA1*0501 with the DQB1 risk allele *0301 was often found in the MVL group. The genotype *0301/*0401-2 was frequently found in the RF and Sydenhamn's chorea patient groups. The haplotype *07-*0201-*0302 was frequently found in RF and homogeneous patient groups, including the MVL group. In addition, haplotypes *04-*0401-*0301 and *04-*0301-*0401-2 were frequent amongst patients with Sydenhamn's chorea. The protective alleles DQA1*0102 and DQB1*0602-8 in the haplotype DRB1*15 were less frequently found in RF patients. The results of the present study support our hypothesis and indicate that certain HLA class II haplotypes are associated with risk for or protection against RHD and that these associations are more evident in patients in clinically homogeneous groups.Peer reviewe

Natural clearance of hepatitis C virus in hemophilia patients

Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Objective. The objective of this study was to investigate the prevalence of HCV (hepatitis C virus) infection in hemophilia patients in Latvia and to analyze association between natural clearance of HCV and human leukocyte antigen (HLA) class II genes. Material and methods. From 61 hemophilic patients participating in this study, 38 were adults and 23 were pediatric patients younger than 18 years. To analyze association between HLA class II alleles and natural clearance of HCV, the gene frequency was compared in hemophilia patients group and the control group of 60 healthy subjects, all men. Serum HCV RNA was qualitatively determined and HLA class II alleles were identified by polymerase chain reaction (PCR) method. Results. HCV infection is common among hemophilia patients in Latvia. Antibodies to HCV were found in 45 of 61 (74%) hemophilia patients. In 41% of hemophilia patients (18 of 44), HCV infection resolved spontaneously. Children cleared HCV more frequently than adults (7 of 11 comparing to 11 of 33, respectively; OR=3.50; P<0.05). The frequency difference was found to be statistically significant when comparing HLA alleles distribution in the sample of hemophilia patients who naturally cleared HCV (n=18) and in the control group (n=60) (corresponding frequency of HLA-DRB1*07 allele - 4 (11.11%) and 9 (1.67%); OR=7.38; P<0.05). Conclusions. Natural clearance of HCV infection is frequently found in hemophilia patients in Latvia. Children are more likely to clear virus naturally than adults. There is an association between natural clearance of HCV and HLA allele DRB1*07 in hemophilia patients.Peer reviewe

HLA B27 allele types in homogeneous groups of juvenile idiopathic arthritis patients in Latvia

Juvenile idiopathic arthritis (JIA) is a heterogeneous condition and therapeutic strategies vary in different JIA types. The routinely accepted practice to start with Sulphasalazine (SS) as the first line treatment in patients with HLA B27 positive JIA proves to be ineffective in a large proportion of children