Isotype analysis of the anti–CENP‐B anticentromere autoantibody: Evidence for restricted clonality

Eisenberg, Robert A.; Earnshaw, William C.; Bordwell, Bonnie J.; Craven, S Y; Cheek, Robert; Rothfield, Naomi F.

doi:10.1002/anr.1780321019

Cited by 13 publications

(6 citation statements)

References 13 publications

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“…Both above mechanisms may be operational in generating scleroderma autoantibodies. We have found evidence that both play a role in the origin of scleroderma autoantibodies [32,33,[41][42][43]. We hypothesize that the scleroderma autoantibodies share a 'specific scleroderma' V H -Id.…”

Section: Introductionmentioning

confidence: 85%

“…In scleroderma we have reported a germ-line gene configuration for an IgM antitopoisomerase-I [41], and evidence of oligoclonality in the anti-CENP-B autoantibodies [42].…”

Section: Introductionmentioning

confidence: 88%

“…The observation that sera from non-related patients who have the same autoantibody bind the same epitope suggests that they have undergone similar autoimmune responses. The shared autoepitope could be the primary target [32,33] that begins a restricted B cell response [41][42][43]. Consequently, one may hypothesize that a process of 'epitope spreading' is responsible for recognition of epitopes (within the CENP-B or topoisomerase-I) [32,[35][36][37][38][39][40], or other autoantigen proteins (CENP-A and or C) [33,43].…”

Section: Introductionmentioning

confidence: 99%

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A cross-reactive idiotype in scleroderma

Vázquez‐Abad

Tian

Zanetti

et al. 1997

Clinical and Experimental Immunology

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SUMMARYAutoantibodies to centromere proteins (anti-CENPs) and to topoisomerase-I are highly specific for scleroderma. Unlike most autoantibodies in other diseases, these autoantibodies are mutually exclusive. We have analysed the idiotypes (Ids) expressed by anti-CENP-B, antitopoisomerase-I, and IgGs from 20 scleroderma patients. Rabbit anti-Ids were prepared to antitopoisomerase-I from two scleroderma patients, and to anti-CENP-B from four patients. These six anti-Ids were used to study the purified autoantibodies from 20 scleroderma patients: four antitopoisomerase-I, 10 anti-CENP-B, and six purified IgG from scleroderma patients who were negative for both autoantibodies. In addition, we studied sera from 40 normal autoantibody-negative controls, and sera and purified immunoglobulins from 17 systemic lupus erythematosus (SLE) patients containing high titres of anti-double-stranded DNA, and/or autoantibodies to extractable nuclear antigens (ENA). Using direct binding, and competitive inhibition ELISAs and immunoblots, we identified an Id present in the heavy chains of all the affinity-purified antitopoisomerase-I, and anti-CENP-B. Interestingly, this Id was also present in the immunoglobulins of the scleroderma patients who had neither of the two autoantibodies. By contrast, cross-reactive Id-EM was not found in the sera or immunoglobulins from 17 SLE patients, or in the sera from 40 normal subjects. Several samples from two patients showed that this cross-reactive Id-EM was stable over time. The scleroderma disease-specific autoantibodies may be identified through a common structural feature at the variable region of the heavy chain: cross-reactive Id-EM.

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Section: Introductionmentioning

confidence: 85%

“…In scleroderma we have reported a germ-line gene configuration for an IgM antitopoisomerase-I [41], and evidence of oligoclonality in the anti-CENP-B autoantibodies [42].…”

Section: Introductionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

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A cross-reactive idiotype in scleroderma

Vázquez‐Abad

Tian

Zanetti

et al. 1997

Clinical and Experimental Immunology

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“…We have not succeeded in narrowing down epitope I under 65 amino acids. Given our observation that IgM-or IgA-class autoantibodies of the longitudinal sera in this study were not found, but that strong IgG-class responses persisted for years along with the restricted clonality in anti-CENP-B response characterized by Eisenberg et al (26), T cells are probably important for their production and immunoregulation.…”

Section: Discussionmentioning

confidence: 40%

The Clinical Expression in Anticentromere Antibody‐positive Patients Is Not Specified by the Epitope Recognition of CENP‐B Antigen

Muro

Sugimoto

Himeno

et al. 1992

The Journal of Dermatology

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Centromere protein B (CENP-B), which is an alphoid DNA binding protein, is the target antigen in autoimmune disease patients (often with scleroderma). From our previous analysis of the reactivity of anticentromere sera, four independent epitopes were identified on recombinant CENP-B. The anticentromere sera displayed heterogeneity in their patterns of reactivity to the four epitopes. We have investigated to what extent this heterogeneity of the target autoepitope on CENP-B accounts for the clinical diversity of anticentromere antibody (ACA)-positive patients. A major autoepitope, epitope I, was recognized by all 40 ACA-positive sera; however, the other three epitopes were recognized differently from case to case. We could not find any significant correlation between the reactivity to CENP-B autoepitopes and the clinical presentation of ACA-positive patients. There was considerable clinical diversity, even among the nine patients showing specificity for the single major autoepitope. In conclusion, we found that, although ACA-positive patients were both clinically and immunologically heterogeneous, in most respects the clinical expression appeared to be independent of the reactivity to the CENP-B autoepitope, a finding which suggests that identification of the target epitope of CENP-B is unlikely to assist in the clinical classification of the disease in ACA-positive patients. The identification of multiple B cell epitopes on CENP-B is consistent with the concept that the self-antigen drives the antibody response. However, factors other than CENP-B autoepitope specificity must determine the clinical expression of ACA responses.

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“…As noted in early studies, CENP-B is an unlikely candidate for selfimmunization due to centromeres accounting for a small portion of the intracellular volume [37]. Regardless, detailed study of the ACA serotype has characterized it as a product of an antigen-driven response resulting in high titers [9,20,45].…”

Section: Autoantibodies Targeting Cenp-b Define Acasmentioning

confidence: 99%

Clinical and Molecular Features of Anti-CENP-B Autoantibodies

Prasad

Bellacosa

Yen

2021

JMP

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Centromeric proteins are the foundation for assembling the kinetochore, a macromolecular complex that is essential for accurate chromosome segregation during mitosis. Anti-centromere antibodies (ACAs) are polyclonal autoantibodies targeting centromeric proteins (CENP-A, CENP-B, CENP-C), predominantly CENP-B, and are highly associated with rheumatologic disease (lcSSc/CREST syndrome). CENP-B autoantibodies have also been reported in cancer patients without symptoms of rheumatologic disease. The rise of oncoimmunotherapy stimulates inquiry into how and why anti-CENP-B autoantibodies are formed. In this review, we describe the clinical correlations between anti-CENP-B autoantibodies, rheumatologic disease, and cancer; the molecular features of CENP-B; possible explanations for autoantigenicity; and, finally, a possible mechanism for induction of autoantibody formation.

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Isotype analysis of the anti–CENP‐B anticentromere autoantibody: Evidence for restricted clonality

Cited by 13 publications

References 13 publications

A cross-reactive idiotype in scleroderma

A cross-reactive idiotype in scleroderma

The Clinical Expression in Anticentromere Antibody‐positive Patients Is Not Specified by the Epitope Recognition of CENP‐B Antigen

Clinical and Molecular Features of Anti-CENP-B Autoantibodies

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