Development of a CENP‐A/CENP‐B–specific immune response in a patient with systemic sclerosis

Mähler, Michael; Mierau, Rudolf; Genth, E.; Blüthner, Martin

doi:10.1002/art.10330

Cited by 26 publications

(15 citation statements)

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“…gradual release of sequestered epitopes [3,[7][8][9][10][11][12][13][14][15][16]. EpsteinBarr virus (EBV) infection might be among the factors that are involved in both rheumatoid arthritis (RA) [17][18][19][20][21][22][23] and in Sjögren syndrome (SS) [24,25].…”

mentioning

confidence: 99%

Elevated immunoglobulin G antibodies to the proline-rich amino-terminal region of Epstein–Barr virus nuclear antigen-2 in sera from patients with systemic connective tissue diseases and from a subgroup of Sjögren's syndrome patients with pulmonary involvements

Yamazaki

Kitamura

Kusano

et al. 2005

Clinical and Experimental Immunology

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SummaryAssociations of Epstein-Barr virus (EBV) and autoimmune diseases have been hypothesized. We have analysed IgG antibodies to EBV nuclear antigen (EBNA)-2 in sera from Japanese patients with autoimmune systemic connective tissue diseases (CTD), exemplified by systemic lupus erythematosus (SLE), primary Sjögren's syndrome (SS), rheumatoid arthritis (RA), systemic sclerosis (SSc) and secondary SS (classical CTDs complicated with SS). An enzyme-linked immunosorbent assay (ELISA) which uses glutathione-Stransferase polypeptides fused to EBV nuclear antigen (EBNA)-2 and EBNA-1 was developed. Ratios of IgG antibody reactivity to whole IgG concentrations of sera were calculated to normalize EBNA-2 and EBNA-1 antibody levels to the hypergammaglobulinaemia that occurs in CTD. The ELISA optical density OD 450 readings of IgG antibodies to both the amino-terminal aa 1-116 of EBNA-2 and carboxyl-terminal aa 451-641 of EBNA-1 were elevated significantly in patients with SLE, primary SS, RA, SSc and secondary SS when compared to EBNA-1. The OD readings were divided by serum IgG concentrations to normalize for the hypergammaglobulinaemia. The specific levels of IgG antibodies to the amino-terminal region of EBNA-2 were elevated in patients with SLE, primary SS or RA, as well as those with secondary SS complicated with SLE or RA. The EBNA-2 amino-terminal region contains a polyproline tract and a proline-rich sequence and has considerable amino acid sequence homology with many cellular proline-rich proteins . High ratios of EBNA-2 aa 1-116 to EBNA-1 aa 451-641 IgG antibody levels which probably suggest reactivation of EBV latent infection were associated significantly with pulmonary involvement in SS patients. These results are consistent with the hypothesis that the sequence similarity between the amino-terminal region of EBNA-2 and proline-rich cellular proteins is associated with pathogenesis in a subpopulation of CTD patients, possibly by the molecular mimicry-epitope shift mechanism.

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confidence: 99%

Elevated immunoglobulin G antibodies to the proline-rich amino-terminal region of Epstein–Barr virus nuclear antigen-2 in sera from patients with systemic connective tissue diseases and from a subgroup of Sjögren's syndrome patients with pulmonary involvements

Yamazaki

Kitamura

Kusano

et al. 2005

Clinical and Experimental Immunology

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“…Also, several correlations between other proteins of the CENP family and autoimmune illnesses have been reported. Mahler et al [27] described a study of systemic sclerosis patients, who developed an antibody response against histone H3 that also induced reactivity against CENP-A and CENP-B through intra- and intermolecular epitope spreading. Other patients with systemic sclerosis have been described to express autoantibodies against CENP-E, CENP-I and CENP-O [28-30].…”

Section: Discussionmentioning

confidence: 99%

Correlation between centromere protein-F autoantibodies and cancer analyzed by enzyme-linked immunosorbent assay

et al. 2013

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BackgroundCentromere protein-F (CENP-F) is a large nuclear protein of 367 kDa, which is involved in multiple mitosis-related events such as proper assembly of the kinetochores, stabilization of heterochromatin, chromosome alignment and mitotic checkpoint signaling. Several studies have shown a correlation between CENP-F and cancer, e.g. the expression of CENP-F has been described to be upregulated in cancer cells. Furthermore, several studies have described a significant correlation between the expression of autoantibodies to CENP-F and cancer.MethodsAutoantibodies to CENP-F were detected in a small number of samples during routine indirect immunofluorescence (IIF) analysis for anti-nuclear antibodies (ANA) using HEp-2 cells as substrate. Using overlapping synthetic peptides covering a predicted structural maintenance of chromosomes (SMC) domain, we developed an enzyme-linked immunosorbent assay (ELISA) for detection of CENP-F antibodies.ResultsAnalyzing the reactivity of the sera positive in IIF for CENP-F antibodies to overlapping CENP-F peptides, we showed that autoantibodies to several peptides correlate with the presence of antibodies to CENP-F and a diagnosis of cancer, as increased CENP-F antibody expression specific for malignant cancer patients to five peptides was found (A9, A12, A14, A16, A27). These antibodies to CENP-F in clinical samples submitted for ANA analysis were found to have a positive predictive value for cancer of 50%. Furthermore, the expression of cancer-correlated CENP-F antibodies seemed to increase as a function of time from diagnosis.ConclusionThese results conform to previous findings that approximately 50% of those patients clinically tested for ANA analyses who express CENP-F antibodies are diagnosed with cancer, confirming that these antibodies may function as circulating tumor markers. Thus, a peptide-based CENP-F ELISA focused on the SMC domain may aid in identifying individuals with a potential cancer.

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“…Anti-Th/To antibodies have been associated with the limited cutaneous form of SSc and with lung disease 8 . Case reports with sequential serum samples are valuable tools to study the evolution of autoantibody responses in autoimmune diseases 9 . We report a case of SSc with seroconversion from anti-Th/To to anti-CENP-B antibodies.…”

Section: To the Editormentioning

confidence: 99%

Seroconversion from Anti-Th/To to Anticentromere Antibodies in a Patient with Systemic Sclerosis

2017

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Development of a CENP‐A/CENP‐B–specific immune response in a patient with systemic sclerosis

Cited by 26 publications

References 15 publications

Elevated immunoglobulin G antibodies to the proline-rich amino-terminal region of Epstein–Barr virus nuclear antigen-2 in sera from patients with systemic connective tissue diseases and from a subgroup of Sjögren's syndrome patients with pulmonary involvements

Elevated immunoglobulin G antibodies to the proline-rich amino-terminal region of Epstein–Barr virus nuclear antigen-2 in sera from patients with systemic connective tissue diseases and from a subgroup of Sjögren's syndrome patients with pulmonary involvements

Correlation between centromere protein-F autoantibodies and cancer analyzed by enzyme-linked immunosorbent assay

Seroconversion from Anti-Th/To to Anticentromere Antibodies in a Patient with Systemic Sclerosis

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