Junko Moriuchi

Combinations of HLA-DPB1 and HLA-DQB1 alleles determine susceptibility to early-onset myasthenia gravis in Japan

HLA class II alleles in the DQA1, DQB1, DRB1, and DPB1 genes were investigated in Japanese patients with myasthenia gravis (MG) by digestion of polymerase chain reaction amplified DNAs with allele specific restriction endonucleases (PCR-RFLP). A significantly higher frequency of DQB1*03, which includes *0301, *0302, *0303 and determines the serological DQ3 specificity, was observed in female patients less than 30 years in age at onset of disease compared with healthy controls (90.5 vs. 53.2%). This study also confirms the high incidence of DPB1*0201 in early-onset female patients compared to the controls (85.7 vs. 40.3%). Moreover, 81.0% of the early onset female patients were found to carry both DQB1*03 and DPB1*0201, compared to 17.7% of the controls. Since DQB1*03 and DPB1*0201 are not in linkage disequilibrium, both these alleles are supposed to be synergistically involved in disease development in early-onset female MG. In contrast, no obvious association of HLA-DQA1, DQB1, DRB1 and DPB1 alleles with either late-onset patients or patients with thymoma was observed. Clearly, the genetic background of Japanese females with early onset MG is different from that of other patients with MG.

Taq I Polymorphism of the Epidermal Growth Factor Receptor Gene in Caucasoids and Japanese

Genetic polymorphism of the epidermal growth factor (EGF) receptor gene following Taq I digestion was compared between samples of genomic DNA from glioma-derived cell lines and Caucasoid and Japanese subjects. The same three allelic forms of the EGF receptor gene, marked by variant fragments of approximately 12.8, 11.6 and 10.8 kb in size were common to both ethnic groups and the 12.8- and 11.6-kb fragments were found in the glioma-derived cell line DNA. A further variant fragment of approximately 13.8 kb in size has been shown to be thus far restricted to the Japanese. These data suggest that most allelic forms of the EGF receptor gene recognized by Taq I restriction fragment length polymorphism have a long evolutionary history and probably do not predispose to development of malignant glioma.

Serum Apolipoprotein H Levels in Systemic Lupus Erythematosus Are Not Influenced by Antiphospholipid Antibodies

Anticardiolipin antibodies (aCL) were recently discovered to recognize a complex consisting of phospholipids and apolipoprotein H (apo H). In this study, we determined the serum apo H levels in 36 systemic lupus erythematosus (SLE) patients with or without antiphospholipid antibodies (aPL), including aCL and lupus anticoagulants, to clarify the possible effects of aPL on apo H levels in vivo. The apo H levels were low in SLE patients as compared with 22 healthy controls. However, no associations were found between apo H levels and circulating aPL or clinical features of the antiphospholipid antibody syndrome. A secondary hyperlipidemic state, which probably related to lupus nephritis (proteinuria) and/or prednisolone treatment, increased apo H levels in SLE patients.

An unusual allelic form of the immunoglobulin lambda constant region genes in the Japanese

The use of DNA probes specific for constant regions of immunoglobulin heavy and light chain genes as well as T-cell receptor (Tcr) subunit genes is now firmly established in the routine diagnosis and classification of non-Hodgkins lymphoma (Arnold et al. 1983; Waldmann et al. 1985; Daus et al. 1989). As detailed by Cossman and co-workers (1988), there are many factors to be considered in interpretation of data derived from molecular biological techniques used in lymphoma classification studies. For example, there is considerable allelism of Tcr and immunoglobulin genes reflected by restriction fragment length polymorphisms (RFLPs) of genomic DNA representing the germline configuration. Consequently, RFLPs marking rare allelic forms of immunoglobulin or Tcr subunit genes may be wrongly interpreted as reflecting monoclonality of a population of cells of lymphoid origin. In Caucasoids, the most common pattern of fragments hybridizing with an immunoglobulin lambda light chain constant region (IGLC2) probe following digestion of genomic DNA with Eco RI comprises fragments with sizes of approximately 8, 14, and 16 kilobases (kb). The 14 and 16 kb fragments are invariant, whereas the 8 kb fragment represents the most frequent allelic form of the IGLC2 genes (Taub et al. 1983; Ghanem et al. 1988). Less frequent allelic forms of the IGLC2 genes are marked by fragments with sizes of approximately 13, 18, or 23 kb. The 13 and 18 kb and probably the 23 kb fragments are due to insertion of 1, 2, or 3 repeats of a 5.2 kb fragment respectively within the 8 kb allele (Taub et al. 1983). Since rare allelic forms of the IGLC2 genes may be misinterpreted as markers of monoclonality in the absence of ap-

A case of systemic lupus erythematosus with various central and peripheral neurological disorders developed with motor paralytic bladder as a major manifestation

A 29-year-old female with systemic lupus erythematosus who developed accerelated hypertension, motor paralytic bladder and various other neurological abnormalities is described. Cystometry demonstrated flaccid atonic neuropathic bladder. Elevated protein level and albuminocytologic dissociation were recognized in her cerebral spinal fluid. Magnetic resonance imaging study detected high signal intensities in themedulla oblongata andcauda equina. Her clinical symptoms and laboratory abnormalities were resolved after two courses of methyl-prednisolone pulse therapy. Possible roles of antiphospholipid antibodies were considered in the pathogenesis of her neurologic abnormalities.