HLA in Japanese Insulin-Dependent Diabetes Mellitus

Ninety-four Japanese patients with insulin-dependent diabetes mellitus (IDDM) and 388 healthy randomly selected Japanese were HLA typed. Significantly increased frequencies of Bw54, Cwl, DR4, B17 (Bw58), DR3 and DRw9 were observed. Simultaneously, the frequencies of Bw52 and DR2 in the patients were found to be significantly low as compared with those in helathy Japanese controls. It was suggested that one of the susceptibility genes to IDDM, which is associated with B8, DR3 haplotypes in Caucasoids, might be associated with B17 (Bw58), DR3 haplotypes in Japanese and in Chinese. Another susceptibility gene to IDDM associated with DR4 in Caucasoids might be associated with both DR4 and DRw9 in Japanese. A very rare variant of properdin factor B allotypes (BF*FT or BF*F075) was shown to be associated significantly with Japanese IDDM and with Bw52, DRw9 haplotypes.     

HLA Class I and Class II HLA DRB Profiles in Egyptian Children with Rheumatic Valvular Disease

Poststreptococcal sequelae, especially acute rheumatic fever/rheumatic heart disease continues to occur in significant proportions in many parts of the world, especially in less developed countries. An important factor in the study of rheumatic heart disease is the human genetic susceptibility to the disease. The aim of the present study was to detect the most prevalent HLA class I and class II types associated with risk of rheumatic heart disease in Egyptian children. Our study was performed on 100 patients with rheumatic valvular heart diseases and 71 control subjects. Patients were recruited from the Heart Institute, Embaba, Egypt. HLA typing for HLA class I was performed by serotyping and HLDR allele genotyping was performed using INNO-LiPA kits. In the study of HLA class I, there was a statistically significant increase in the B5 allele (P = 0.03; odds ratio, 3.46 [1.12–10.72]) in patients compared to controls, while B49 and B52 alleles (P = 0.004 and P = 0.02) were found in controls only. There was a statistically significant increase in HLA DR* 04-02, 3.46 (1.12–10.72) and HLA DR *10-0101 5.75 (1.27–25.98) in patients. Meanwhile HLA DR*1309120 was found only in controls (P = 0.02). Our study provides further information on the genetic predisposition for rheumatic valvular disease and the protective genotypes in rheumatic heart disease. Further insight into the molecular mechanisms of the disease will be a useful tool for predicting clinical outcome in those patients and, thus, potentially offer new means and approaches to treatment and prophylaxis, including a potential vaccine.     

Acute rheumatic fever and poststreptococcal acute glomerulonephritis caused by T serotype 12 Streptococcus

We present a rare case of a 10 year old Japanese boy with acute rheumatic fever accompanied with poststreptococcal acute glomerulonephritis. We isolated group A Streptococcus serotype T 12, a strain that was thought to be nephritogenic but not rheumatogenic, from throat culture. Although rare, physicians should be aware that acute renal disease may accompany rheumatic fever.     

The Study of HLA, ICA and Autoantibodies in Japanese Type 1 Diabetes Mellitus

HLA, ICA (islet cell antibody) and autoantibodies were studied in 65 Japanese patients with type 1 diabetes mellitus to elucidate the existence of immuno-genetic heterogeneity. Patients with autoantibodies had increased frequencies of HLA DRw9 antigen and of HLA haplotype of Bw61-DRw9, and a slow decay of ICA, while patients without autoantibodies had increased frequencies of HLA DR4 antigen and of HLA haplotype of Bw54-DR4, and a rapid decay of ICA. These findings support the concept of immunogenetic heterogeneity in Japanese type 1 diabetes mellitus.     

Sweet’s syndrome in a neonate with non-B54 types of human leukocyte antigen

Background

Sweet??s syndrome (acute febrile neutrophilic dermatosis) is characterized by fever, polymorphonuclear leukocytosis of blood, painful plaques on the limbs, face and neck, and histologically a dense dermal infiltration with mature neutrophils. Sweet??s syndrome is often a complication of hematologic malignant disease or drug-induced sensitivity reactions and has a significant susceptibility correlated with certain human leukocyte antigen (HLA).

Methods

A 5-week-old Japanese girl with Sweet??s syndrome confirmed by skin biopsy was successfully treated and HLA analysis was performed.

Results

The patient was one of the youngest patients reported with Sweet??s syndrome, suggesting the importance of the genetic background. Although the HLA types of the patient did not have B54, which was reported as a significant susceptibility correlation, structural analysis of the patient??s HLAs suggested a similar possible motif for the bound peptides.

Conclusion

Studies on the HLA bound peptides and HLA structural analysis for patients with Sweet??s syndrome would be valuable for understanding the molecular mechanism of the pathogenesis.     

Twins with moyamoya disease

Moyamoya disease is a progressive disease which involves the internal carotid arteries and its branches bilaterally. The disease is reported both in adults and in children. Moyamoya disease is frequently seen in Japanese patients having certain human leucocyte antigen (HLA) haplotypes including HLA-Aw24, Bw46 and Bw54. Twin cases are rarely reported in the literature. We hereby present the first Turkish monozygotic twins with moyamoya disease whose HLA haplotypes are A2, A9, B21, Bw22, Bw4, Bw6, Cw3, and DR2, DR4, DRw52, DRw53, Dq7. The patients with advanced disease were given nifedipine and intravenous immunoglobulin (400mg/kg/d for 5 days). During the 11 months of follow-up, the patients were attack free.     

Atrioventricular conduction in children with acute rheumatic fever.

Atrioventricular conduction was quantitatively evaluated in 118 children with acute rheumatic fever. The mean PR index in children with acute rheumatic fever, 1.06 +/- 0.38, was significantly higher than normal children or children who had febrile illness of nonrheumatic or nonstreptococcal origin (P is less than .001). Among 35 children with rheumatic fever and an abnormal PR index, the disease presented as carditis in 21, arthritis in ten, and chorea in four. The mean PR index and the frequency distribution of abnormal PR indices were significantly higher in children with carditis (P is less than .001). Five children who initially had an abnormal PR index and arthritis or chorea subsequently developed carditis. These observations suggest that children with acute rheumatic fever and abnormal PR index warrant close observation for possible clinical evidence of myocardial involvement during subsequent course of the illness.     

Sister-chromatid exchange analysis on long-term benzathine penicillin for secondary prophylaxis of rheumatic fever

A single intra-muscular injection of 1.2 millions units of benzathine penicillin every 4 weeks is the most widely used method for the antibiotic prophylaxis of rheumatic fever. The aim of this study is to evaluate the effect of long-term benzathine penicillin on DNA in patients with rheumatic fever. Thirty children with confirmed rheumatic fever who were on the benzathine penicillin prophylaxis were enrolled in the study, and 30 similar normal children served as a control group. To detect any DNA damage, SCE analysis were performed in circulating lymphocytes of the subjects. A statistically significant increased frequency of SCE was observed in children on the benzathine penicillin prophylaxis (no = 30, mean SCEs / cell ± SD 7.54 ± 1.81 ) as compared to a control group (no = 30, mean SCEs / cell ± SD 5.82 ± 1.40). It has been suggested that the difference in the SCE frequencies was induced by the administration of the benzathine penicillin for a long time, and further investigations are needed to confirm this toxic effect.     

HLA and rheumatic fever in Turkish children

Summary We report the results of research on human leukocyte allo-antigen (HLA) and rheumatic fever (RF), the first published study to be carried out among Turkish children with RF. Ninety-three Turkish children, aged between 6 and 16 years(mean: 8±2.6), with RF participated in the study. Of the total, 26 patients had their first attack and 39 had acute rheumatic activity at the time of registration. The results demonstrate (1) negative but not significant association between HLA-A2 and RF; (2) a positive association between HLA-DR4 and RF (p<0.001); (3) a significant association between HLA-DR4 and carditis, but not with isolated arthritis. These results corroborate the concept of race-specific genetically determined familial susceptibility to the development of rheumatic heart disease.     

Polymorphisms of Human Leukocyte Antigen Genes in Korean Children with Kawasaki Disease

Background Kawasaki disease is a leading cause of acquired heart disease in children. The prevalence rate varies in different ethnic groups. Recently, with the clinical application of molecular genetic technology, human leukocyte antigen (HLA) polymorphisms associated with several diseases have been identified by DNA analysis. This study aimed to assess the association of HLA alleles with susceptibility and complications of Kawasaki disease in Korean children. Methods In this study, DNA was extracted from 74 children with a diagnosis of Kawasaki disease. The polymorphisms of the HLA-A, -B, -C, and -DRB1 alleles of patients with Kawasaki disease were determined by polymerase chain reaction (PCR)–amplification refractory mutation system (ARMS) and PCR–sequence-specific primer (SSP) analysis. The polymorphisms identified were compared with those of 159 normal healthy control subjects. Results There was a significant increase in the frequencies of the HLA-B35, -B75, and -Cw09 alleles in patients with Kawasaki disease compared with the healthy control group. There was no increase in the frequency of HLA-DRB1 alleles among the Kawasaki disease patients compared with a healthy control group. When the patients with Kawasaki disease were divided into two subgroups, with or without coronary complications, the Kawasaki disease patients with coronary complications showed a significantly increased frequency of the HLA-DRB1*11 allele compared with the healthy control group and increased frequency of HLA-DRB1*09 in a comparison of the subgroups. Conclusions This study suggests that polymorphisms in some alleles of B and C in HLA class I genes are associated with Kawasaki disease in Korean children.     

Acute rheumatic fever in a patient with glycogen storage disease type Ib: causal or coincidental simultaneous occurrence?

We report a Caucasian female who was diagnosed with glycogen storage disease type Ib (GSD-Ib) at the age of 4 months and whose clinical course was complicated by neutropenia and very frequent episodes of infection, including tonsillopharyngitis. Recurrent group A streptococcal infections resulted in multiple episodes of extremely high serum levels of antibodies to streptolysin O (5,000 IU/ml) and DNAse B (6,000 IU/ ml). At the age of 14 years she presented with carditis, migratory arthritis, fever, elevated erythrocyte sedimentation rate as well as serological evidence for recent streptococcal infection providing a diagnosis of acute rheumatic fever. CONCLUSION: the occurrence of these two very rare disorders in our patient may indicate that this association is not coincidental because neutrophil dysfunction in glycogen storage disease type Ib may have predisposed this patient to acute rheumatic fever due to increased susceptibility to group A streptococcal infections. aberrant glycogenolysis and gluconeogenesis, neutropenia and neutrophil dysfunction are regular findings in GSD-Ib. Neutropenia and neutrophil dysfunction in patients with GSD-Ib are due to defects in myeloid maturation, impaired neutrophil motility, defective chemotaxis and phagocytosis and diminished bactericidal activity resulting in recurrent bacterial infections.     

Rheumatic fever in childhood--today

Acute rheumatic fever in the young: a review of historical land marks and the current status of rheumatic fever are discussed. The follows are presented here: prevent-day epidemiology; the role of group A streptococcus and the reappearance of "rheumatogenic" serotypes; the host's susceptibility and the tantalizing possibility of a genetic basis; the basis of autoimmune pathogenesis (so-called molecular mimicry); the increasing diagnostic difficulties and the critical review of Jones criteria; the reassessment of primary prevention and the couvent possibility of a streptococcal vaccine.     

Naproxen as an alternative to aspirin for the treatment of arthritis of rheumatic fever: a randomized trial

We performed a prospective, randomized, open-label equivalence study comparing the use of naproxen to aspirin in 33 patients with rheumatic fever. The mean time until resolution of arthritis was 2.9+/-2.9 days in both groups. Liver enzyme elevations were more frequent in the aspirin group (P=.002). We conclude that naproxen is as effective, is easier to use, and is safer than aspirin in the treatment of the arthritis of rheumatic fever.     

Dermatoglyphic alterations associated with acute rheumatic fever in children

The dermatoglyphic configurations of 78 children with acute rheumatic fever were compared with those of 46 first-degree relatives and 1,310 normal subjects. Of the children with acute rheumatic fever, 75% had an ulnar deviation of the axial triradius. In about 40% of this group, the ulnar deviation was associated with a concomitant distal displacement, which resulted in a significantly higher mean maximal angle atd (P less than .001) and significantly lower mean ab and td ridge counts (P less than .001) relative to normal control values. The palmar dermatoglyphics of patients with acute rheumatic fever were more closely related to the configurations of first-degree relatives than to normal controls. The dermatoglyphic profiles of six patients were nearly identical to those of their first-degree relatives, all of whom had a history of acute rheumatic fever. Presence of abnormal dermatoglyphic profiles in a large proportion of children with acute rheumatic fever supports the hypothesis that certain individuals have a genetic predisposition to this disease.     

Acute rheumatic fever without early carditis: an atypical clinical presentation

The original Jones criteria, first introduced in 1944, have been modified four times and updated-revised criteria were published in 1992. A variety of clinical manifestations, which may be the presenting signs and symptoms of acute rheumatic fever, are not included in the updated-revised Jones criteria. A retrospective study was conducted on all children previously diagnosed to have acute rheumatic fever between September 1998 and September 2002. Review was focused on clinical presentation; out of 60 medical records reviewed, 4 patients with unusual clinical presentation were recognised and are reported here to highlight the potential diagnostic problems of acute rheumatic fever. They presented with atypical articular involvement, silent carditis and low-grade fever in the presence some time of a positive family history for rheumatic fever. Conclusion:a high index of suspicion and an awareness of the absence of early carditis are necessary to make the diagnosis of acute rheumatic fever.Abbreviations ARF acute rheumatic fever - PSReA post-streptococcal reactive arthritis - RF rheumatic fever     

儿童风湿热及风湿性心瓣膜病85例临床分析

为观察儿童风湿热及风湿性心瓣膜病临床动态变化趋势,分析本院90年代诊治的85例风湿热及心瓣膜病发生状况、临床特点和治疗预防复发情况。结果示本组风湿热造成急性心瓣膜炎占77.65%,首诊慢性心瓣膜病占22.35%,其中三分之二患儿以往无急性风湿热病史。首次发病复发率为14.12%,风湿活动复发常以不同程度心力衰竭（心衰）症状就诊,激素抗风湿治疗能够迅速缓解急性心脏炎和改善心功能。1例反复风湿活动顽固性心力衰竭接受二尖瓣置换术效果甚佳。结果表明,减少儿童风湿性心瓣膜病形成不仅要控制急性风湿热,而且需要及时发现潜隐的风湿活动。     

Coxsackie virus infections in rheumatic fever

The close relationship between Group A beta Hemolytic Streptococci (GABS) and rheumatic fever is a well established one. However, the concept of the streptococcus as the sole etiologic agent of the rheumatic heart disease (RHD) has been challenged over the past years. Since coxsackievirus group B (CVB) has long been proposed as a cause of acquired valvular disease simulating rheumatic fever, we attempted in this study to document infections with this group of viruses in patients with rheumatic fever. We obtained blood samples from 106 patients with old (quiescent) rheumatic fever/rheumatic heart disease [group I], 94 patients with acute rheumatic fever (ARF) [group II], and 74 normal matched controls. We tested for the presence of neutralizing antibodies to the 6 serotypes of CVB by a micro neutralization test. We have found that infection with CVB, especially types B2 and B4, was common in the studied population. Forty two percent of normal individuals had evidence of infection with any of the 6 serotypes of CVB. Patients of group I had significantly more frequent infections with CVB 2. Patients in group II had significantly more frequent infections with CVB 2 and CVB 6. There was no clear correlation between such infections and the clinical course of rheumatic fever. There was no difference in the incidence of CVB infections between patients with definite ARF, and patients with suspected ARF. We set a low order association between rheumatic fever and infection with CVB types B2 and B6. We emphasize the importance of pursuing the investigation of the role of CVB in relation to RHD.