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The soluble CTLA-4 receptor: a new marker in autoimmune diseases

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Pawlak E., Kochanowska I. E., Frydecka I., Kielbinski M., Potoczek S., Bilinska M.

Archivum Immunologiae et Therapiae Experimentalis

2005

vol. 53

issue 4

336-341

A soluble form of cytotoxic T lymphocyte-associated antigen-4 (sCTLA-4) was recently found and shown to possess B7 binding activity. sCTLA-4 is generated by alternatively spliced mRNA. The mRNA encoding sCTLA-4 consists of 3 exons: exon 1 encodes a leader peptide, exon 2 the ligand binding domain, and exon 4 the cytoplasmic tail, but it lacks the transmembrane domain encoded by exon 3. The altered transcript is detected in resting CD4 and CD8 T cells and its expression is inhibited after 24?48 h of activation and returns to the prestimulation level after 72?120 h of activation. Low levels of sCTLA-4 have been detected in normal human serum and increased serum levels have been observed in several autoimmune diseases (e.g. Graves' disease, myasthenia gravis, systemic lupus erythematosus, and systemic sclerosis). The biological significance of increased sCTLA-4 serum level has not been clarified. On one hand, sCTLA-4 may bind B7 expressed on antigen-presenting cells and is thus able to interfere with the B7:CD28-mediated costimulation of T cell responses. On the other hand, sCTLA-4 may also be capable of interfering with B7:CTLA-4 interactions, thereby blocking the negative signal imparted via the full-length form of CTLA-4. This double-edged nature of B7 blocking by sCTLA-4 may result in different outcomes of the clinical course of disease.

Lack of association between Exon 1 CTLA-4 gene polymorphism A(49)G and multiple sclerosis in Polish population of the Lower Silesia Region

84%

Bocko D., Bilinska M., Dobosz T., Zoledziewska M., Suwalska K., Tutak A., Gruszka E., Frydecka I.

Archivum Immunologiae et Therapiae Experimentalis

2003

vol. 51

issue 3

201-205

Multiple sclerosis (MS) a chronic inflammatory demyelinating disease of the central nervous system (CNS) is believed to have a T-cell mediated autoimmune etiology. The cytotoxic T lymphocyte antigen 4 (CTLA-4) gene is a strong candidate for the involvement in autoimmune diseases because CTLA-4 plays an important role in downregulation of early and late stages of T cell activation and maintenance of peripheral T cell tolerance. To examine the genetic association of the CTLA-4 gene locus with MS, we analyzed exon 1 CTLA-4 gen polymorphism A(49)G in 102 unrelated Polish MS patients in Lower Silesia region and 101 age and sex matched healthy subjects. The distribution of CTLA-4 exon 1 A(49)G genotype, phenotype and allele frequencies did not differ between patients with MS and healthy subjects.

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2 Archivum Immunologiae et Therapiae Experimentalis

1 2005

1 2003

2 Bilinska M.

2 Frydecka I.

1 Bocko D.

1 Dobosz T.

1 Gruszka E.

1 Kielbinski M.

1 Kochanowska I. E.

1 Pawlak E.

1 Potoczek S.

1 Suwalska K.

1 Tutak A.

1 Zoledziewska M.

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The soluble CTLA-4 receptor: a new marker in autoimmune diseases

Lack of association between Exon 1 CTLA-4 gene polymorphism A(49)G and multiple sclerosis in Polish population of the Lower Silesia Region