תרומתי לרפואה

נוגדנים כנגד DNA

עבודות בנושא נוגדנים ל- DNA ניתן למצוא ברשימת המאמרים המלאה, במאמרים הבאים: 29, 40, 52, 58, 62, 76. (לרשימת המאמרים המלאה). להלן, מובאים תקצירים של 5 מאמרים נבחרים:

1. J Immunol. 1991 Oct 15;147(8):2771-6.
Characterization of the human Ig V lambda II gene family and analysis of V lambda II and C lambda polymorphism in systemic lupus erythematosus.
Paul E, Livneh A, Manheimer-Lory AJ, Diamond B.

Abstract
We report the cDNA sequence of an expressed human V lambda II gene and present an RFLP analysis of the Ig gene family defined by this clone. This V lambda II gene was expressed in a monoclonal B cell line generated from a patient with SLE by transformation with EBV. The encoded lambda L chain displays the 8.12 Id, an Id common to anti-DNA antibodies from patients with SLE. Using a coding region probe we estimate from Southern blot analysis that the germline V lambda II gene family contains at least 15 members. Many of the V lambda II restriction fragments are polymorphic both in SLE patients and in nonautoimmune individuals. EcoRI, HindIII, and TaqI RFLP analyses of the V lambda II gene family and EcoRI analysis of the C lambda gene family reveal no polymorphisms specific to SLE. Observed V lambda II and C lambda allele frequencies are the same among SLE patients and nonautoimmune individuals, and show no evidence of linkage disequilibrium between the two loci.

2. J Clin Immunol. 1992 Jan;12(1):11-6.
Lupus anti-DNA antibodies bearing the 8.12 idiotype appear to be somatically mutated.
Livneh A, Behar E, Many A, Ehrenfeld M, Gazit E, Diamond B.

Abstract
Anti-DNA antibodies in systemic lupus erythematosus (SLE) sera were analyzed using an antiidiotype designated 8.12 which recognizes a determinant on lambda light chains highly expressed in SLE sera. Eight of ten normal individuals had peripheral blood lymphocytes which produced high-titered 8.12-positive antibodies, following transformation with Epstein Barr virus, implying that the 8.12-reactive sequence originates in the germline gene (GLG). Of 58 SLE sera, 32 contained elevated titers of 8.12-reactive antibodies. Twenty-three of these sera had 8.12-reactive anti-DNA antibodies, suggesting a strong correlation between 8.12 idiotype and DNA binding. Moreover, 20 of 26 8.12-reactive IgG antibodies and only 4 of 10 8.12-reactive IgM antibodies bound DNA (P less than 0.05). These observations strengthen our previous findings in myeloma sera that DNA binding is associated with IgG isotype in the 8.12 idiotype system and suggest that the acquisition of anti-DNA reactivity in antibodies bearing the GLG idiotype 8.12 is achieved by somatic mutation, a feature of an antigen-driven response.

3. J Immunol. 1992 Dec 1;149(11):3588-95.
The anti-DNA-associated idiotype 8.12 is encoded by the V lambda II gene family and maps to the vicinity of L chain CDR1.
Paul E, Iliev AA, Livneh A, Diamond B.

Abstract    
The 8.12 idiotype is an anti-DNA-associated Id present on lambda L chains that are expressed at high titers in 50% of patients with systemic lupus erythematosus. Since this Id can be present on as much as a third of a patient's anti-DNA antibodies and is found in renal glomeruli, 8.12 is thought to be a marker for a subset of pathogenic anti-DNA auto-antibodies. A molecular analysis of the 8.12 positive antibodies was designed to explore the genetic basis of this Id. Monoclonal human B cell lines were generated by transformation with EBV and lambda L chain-secreting lines were analyzed for Id expression and V region gene usage. In this panel of Ig lambda cell lines, the 8.12 idiotype is encoded exclusively by members of the V lambda II gene family. The sequences of several 8.12+ and 8.12- V lambda II genes are reported here and are used to map the 8.12 Id to the vicinity of CDR1, as well as to further characterize the large and polymorphic V lambda II gene family.

4. Clin Immunol Immunopathol. 1993 Jul;68(1):68-73.
Anti-DNA antibodies secreted by peripheral B cells of lupus patients have both normal and lupus-specific features.
Livneh A, Or G, Many A, Gazit E, Diamond B.

Abstract
Autoantibodies present in sera of patients with systemic lupus erythematosus (SLE) are found in low titer in sera of healthy individuals. Hence, it is possible that B cell populations in SLE patients and in normal individuals are homologous and in the absence of regulatory forces would secrete similar antibodies. We therefore studied antibody secretion of Epstein-Barr virus-transformed B cells of 20 SLE patients and 20 healthy subjects. Normal and lupus antibody repertoires did not differ significantly with respect to antigenic specificities, isotype, avidity, and titer. However, anti-DNA antibodies bearing the anti-DNA-associated idiotype 8.12 were found only in SLE. These findings suggest that the B cell repertoire of SLE and normal individuals is more similar than the serum antibody profile. However, part of the anti-DNA response in SLE probably reflects affinity (antigen driven) maturation as it differs in idiotype profile from anti-DNA response of normal individuals.

5. Clin Immunol Immunopathol. 1993 Jul;68(1):68-73.
Anti-DNA antibodies secreted by peripheral B cells of lupus patients have both normal and lupus-specific features.
Livneh A, Or G, Many A, Gazit E, Diamond B.

Abstract
Autoantibodies present in sera of patients with systemic lupus erythematosus (SLE) are found in low titer in sera of healthy individuals. Hence, it is possible that B cell populations in SLE patients and in normal individuals are homologous and in the absence of regulatory forces would secrete similar antibodies. We therefore studied antibody secretion of Epstein-Barr virus-transformed B cells of 20 SLE patients and 20 healthy subjects. Normal and lupus antibody repertoires did not differ significantly with respect to antigenic specificities, isotype, avidity, and titer. However, anti-DNA antibodies bearing the anti-DNA-associated idiotype 8.12 were found only in SLE. These findings suggest that the B cell repertoire of SLE and normal individuals is more similar than the serum antibody profile. However, part of the anti-DNA response in SLE probably reflects affinity (antigen driven) maturation as it differs in idiotype profile from anti-DNA response of normal individuals.

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