HLA-DQ associations and T-cell receptor V-gene usage in peripheral blood of Swedish myasthenia gravis patients.
To characterize better the functional aspects of the HLA class II associations with myasthenia gravis (MG), T-cell receptor (TCR) V alpha/beta elements were studied in peripheral blood in 29 Swedish MG patients. HLA typing had previously been done using polymerase chain reaction with sequence-specific primers (PCR-SSP) or combined with sequence-specific oligonucleotide probes (PCR-SSO). The TCR V gene expression was determined by fluorescence-activated cell sorter (FACS) analysis using 12 monoclonal antibodies (mAb) that detected 30-40% of CD4+ and CD8+ T cells. No correlation between HLA-DQ genotype and TCR V elements could be found, nor was any restricted V gene usage seen. Fourteen (48%) of the patients had T cells showing signs of abnormal expansion in peripheral blood. There was an increased expression of TCR V gene elements in CD8+ T cells in patients (13/29) compared with CD4+ T cells in patients (5/29) (P < 0.05) and in unthymectomized patients compared with controls (14/56) (P < 0.005). TCR V gene expression was also increased in the CD8+ population in unthymectomized (7/8) compared with thymectomized patients (6/21) (P < 0.01). There was an increased expression in both CD4+ and CD8+ populations in unthymectomized patients (7/8, 88%), compared with thymectomized patients (7/21) (P < 0.05). We conclude that the abnormal T-cell expansion in peripheral blood could be a reflection of non-specific pathogenic processes in the muscle and thymus.
Hjelmström
P
P
Department of Medicine and ,Department of Molecular Medicine, Karolinska Hospital, ,Microbiology and Tumour Biology Centre, and ,Department of Neurology, Söder Hospital, Karolinska Institute, Stockholm, Sweden.
Giscombe
R
R
Department of Medicine and ,Department of Molecular Medicine, Karolinska Hospital, ,Microbiology and Tumour Biology Centre, and ,Department of Neurology, Söder Hospital, Karolinska Institute, Stockholm, Sweden.
Lefvert
A K
AK
Department of Medicine and ,Department of Molecular Medicine, Karolinska Hospital, ,Microbiology and Tumour Biology Centre, and ,Department of Neurology, Söder Hospital, Karolinska Institute, Stockholm, Sweden.
Grünewald
J
J
Department of Medicine and ,Department of Molecular Medicine, Karolinska Hospital, ,Microbiology and Tumour Biology Centre, and ,Department of Neurology, Söder Hospital, Karolinska Institute, Stockholm, Sweden.
Pirskanen
R
R
Department of Medicine and ,Department of Molecular Medicine, Karolinska Hospital, ,Microbiology and Tumour Biology Centre, and ,Department of Neurology, Söder Hospital, Karolinska Institute, Stockholm, Sweden.
Sanjeevi
C B
CB
Department of Medicine and ,Department of Molecular Medicine, Karolinska Hospital, ,Microbiology and Tumour Biology Centre, and ,Department of Neurology, Söder Hospital, Karolinska Institute, Stockholm, Sweden.
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000911:Antibodies, Monoclonal; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D005260:Female; D005787:Gene Frequency; D006683:HLA-DQ Antigens; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D018709:Statistics, Nonparametric; D013548:Sweden; D016176:T-Lymphocyte Subsets; D044465:White People / Q000235:genetics
D000911:Antibodies, Monoclonal; D006683:HLA-DQ Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta