Analysis of autoantibodies to recombinant La (SS-B) peptides in systemic lupus erythematosus and primary Sjogren's syndrome.

Bini, P; Chu, Jia Li; Okolo, Chidinma; Elkon, Keith B.

doi:10.1172/jci114441

Cited by 50 publications

(33 citation statements)

References 55 publications

(32 reference statements)

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“…St Clair et al [6], using fusion proteins encoded by La/SSB cDNA fragments, defined three antigenic regions comprising the sequences 1-107, 111-242 and 242-408 (called LaA, LaC and LaD), respectively. More recently, Bini et al [7] defined two immunodominant epitopes, one each in the N-and C-terminal halves of the protein.…”

Section: Introductionmentioning

confidence: 99%

Fine specificity of autoantibodies to La/SSB: epitope mapping, and characterization

Tzioufas

Yiannaki

Sakarellos‐Daitsiotis

et al. 1997

Clinical and Experimental Immunology

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SUMMARYThe B cell epitope mapping of La/SSB was performed using 20 mer synthetic peptides overlapping by eight amino acids covering the whole sequence of the protein. IgG, purified from sera of five patients with systemic lupus erythematosus (SLE) and four sera from patients with primary Sjögren's syndrome (pSS) were tested against the overlapping synthetic peptides. Peptides highly reactive with purified IgG were those spanning the regions 145-164, 289-308, 301-320 and 349-368 364 . Predicted features and molecular similarities of the defined epitopes were investigated using protein databases. The La epitope 147 HKAFKGSI 154 presented 83·3% similarity with the 139 HKGFKGVD 146 region of human myelin basic protein (MBP) and 72% similarity with the fragment YKNFKGTI of human DNA topoisomerase II. Peptides corresponding to these sequences cross-reacted with anti-La/SSB antibodies. Sixty-three sera with anti-La/SSB antibodies from patients with pSS or SLE, 35 sera without anti-La/SSB antibodies from patients with SS or SLE and 41 sera from age/sex-matched healthy blood donors were tested against biotinylated synthetic epitope analogues in order to determine their sensitivity and specificity for the detection of anti-La/SSB antibodies. Anti-La/SSB were detected with various frequencies ranging from 20% to epitope 147 HKAFKGSI 154 to 100% to epitope 349 GSGKGKVQGKKTKF 364 . The overall sensitivity and specificity using all assays with the synthetic peptides were found to be 93·6% and 85·6%, respectively. In conclusion, antibodies to La/SSB constitute a heterogeneous population, directed against different linear B cell epitopes of the molecule. The epitope 147 HKAFKGSI 154 presents molecular similarity with fragments of two other autoantigens, i.e. human MBP and DNA topoisomerase II. Finally, synthetic epitope analogues exhibit high sensitivity and specificity for the detection of anti-La/SSB antibodies.

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Section: Introductionmentioning

confidence: 99%

Fine specificity of autoantibodies to La/SSB: epitope mapping, and characterization

Tzioufas

Yiannaki

Sakarellos‐Daitsiotis

et al. 1997

Clinical and Experimental Immunology

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“…In autoimmune diseases such as Sjogren's syndrome or SLE, the human B cell response to the La/SS-B autoantigen is directed to multiple epitopes that span the full length of the La/ SS-B polypeptide (1)(2)(3)(4)(5)(6)(7). An immunodominant, discontinuous epitope has been identified at the NH2 terminus (LaA; amino acids [aa ]' -107) and may be recognized early in the response (8).…”

Section: Introductionmentioning

confidence: 99%

Identification of a human-specific epitope in a conserved region of the La/SS-B autoantigen.

et al. 1993

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Human anti-La/SS-B autoantibodies are known to react with highly conserved epitopes suggested to be functional or active sites on the La/SS-B polypeptide. This study was designed to determine whether the autoantibodies also react with poorly conserved regions of La/SS-B as predicted by an antigendriven autoimmune response. Binding of human autoantibodies to purified human, mouse, and bovine recombinant fragments representing immunodominant regions of the La/SS-B polypeptide was compared using Western blotting and ELISA. A cross-reactive epitope was located in the highly conserved NH2-terminal region of La/SS-B. Significantly, human-specific epitopes were identified in both the conserved RNA-recognition motif and a poorly conserved COOH-terminal fragment, providing direct evidence for an autoantigen-driven response. The lack of autoantibody cross-reactivity with a conserved domain of mouse and bovine La/ SS-B implies that a small number of residues in human autoepitopes may be critical for autoimmunogenicity. (J. Clin. Invest. 1993Invest. . 92:1104Invest. -1108

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“…The three main theories proposed for autoantibody production have been polyclonal B cell activation (1,2), molecular mimicry with self (3,4), and a response initiated and maintained by self (5,6). While evidence for polyclonal B cell activation exists for some autoantibody responses (1), a number of studies utilizing recombinant nuclear autoantigens (7)(8)(9)(10)(11)(12)(13)(14)(15)(16) have provided strong evidence that ANA responses are induced and maintained by self antigen.…”

Section: Introductionmentioning

confidence: 99%

Definition of a discontinuous immunodominant epitope at the NH2 terminus of the La/SS-B ribonucleoprotein autoantigen.

McNeilage¹,

Umapathysivam²,

Macmillan³

et al. 1992

J. Clin. Invest.

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High-titer IgG autoantibodies to the La/SS-B ribonucleoprotein (RNP) are a hallmark of patients with primary Sjogren's syndrome. Anti-La/SS-B-positive human sera bind to multiple epitopes on recombinant La/SS-B, although the initial response is against an immunodominant epitope within the first 107 NH2-terminal amino acids (aa). Sequence analysis has identified a striking homology between aa 88-101 in this NH2-terminal region of La/SS-B and a feline retroviral gag polypeptide suggesting the anti-La/SS-B response may be initiated by cross-reactivity with an exogenous agent. In the present study, detailed mapping of this NH2-terminal epitope, using recombinant La/SS-B purified from the expression of overlapping DNA fragments spanning aa 1-107, has shown that this immunodominant epitope is a complex conformational or discontinuous epitope dependent upon both aa 12-28 and 82-99 for expression, even though these regions share no homology with each other. This requirement questions the significance of the homology between La/SS-B and a retroviral gag polypeptide in the generation of the B cell response to La/SS-B and is in accord with the general concept that B cells recognize conformational epitopes on antigens rather than small linear peptide sequences. The finding also reinforces the notion that native autoantigen could be the initiator of the autoimmune response. (J. Clin. Invest. 1992. 89:1652-1656

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Analysis of autoantibodies to recombinant La (SS-B) peptides in systemic lupus erythematosus and primary Sjogren's syndrome.

Cited by 50 publications

References 55 publications

Fine specificity of autoantibodies to La/SSB: epitope mapping, and characterization

Fine specificity of autoantibodies to La/SSB: epitope mapping, and characterization

Identification of a human-specific epitope in a conserved region of the La/SS-B autoantigen.

Definition of a discontinuous immunodominant epitope at the NH2 terminus of the La/SS-B ribonucleoprotein autoantigen.

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