Clinicolaboratory characteristics of patients with primary biliary cirrhosis associated with CREST symptoms

Tojo, Jun; Ohira, Hiromasa; Suzuki, Tomohiro; Takeda, Isao; Shoji, Ikuo; Kojima, Toshihiko; Toru, Takeshi; Kuroda, Masashi; Miyata, Masayuki; Nishimaki, Tomoe; Ohnami, Kozo; Kanno, Takashi; Mukai, Shinji; Kasukawa, Reiji

doi:10.1016/s1386-6346(01)00138-3

Cited by 35 publications

(42 citation statements)

References 24 publications

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“…During the last two decades, recombinant CENP-B expressed in E. coli or insect cells had become the antigen of choice in immunoassays that were intended to confirm the presence of ACA reactivity initially identified by an IIF screening test on HEp-2 cells [1,17,22]. A controversy arose when individual studies reported ACA in diseases other than SSc such as SLE, SjS and PBC [2-4,6-10]. Although the prevalence of ACAs is 20 to 40% in SSc and only 3 to 5% in SLE, it has been suggested that numerically more patients with ACAs would actually suffer from SLE than from SSc because SLE is a much more prevalent condition than SSc.…”

Section: Discussionmentioning

confidence: 99%

Clinical and serological evaluation of a novel CENP-A peptide based ELISA

Mähler

Maes²,

Blockmans³

et al. 2010

Arthritis Res Ther

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IntroductionAnti-centromere antibodies (ACA) are useful biomarkers in the diagnosis of systemic sclerosis (SSc). ACA are found in 20 to 40% of SSc patients and, albeit with lower prevalence, in patients with other systemic autoimmune rheumatic diseases. Historically, ACA were detected by indirect immunofluorescence (IIF) on HEp-2 cells and confirmed by immunoassays using recombinant CENP-B. The objective of this study was to evaluate a novel CENP-A peptide ELISA.MethodsSera collected from SSc patients (n = 334) and various other diseases (n = 619) and from healthy controls (n = 175) were tested for anti-CENP-A antibodies by the novel CENP-A enzyme linked immunosorbent assay (ELISA). Furthermore, ACA were determined in the disease cohorts by IIF (ImmunoConcepts, Sacramento, CA, USA), CENP-B ELISA (Dr. Fooke), EliA® CENP (Phadia, Freiburg, Germany) and line-immunoassay (LIA, Mikrogen, Neuried, Germany). Serological and clinical associations of anti-CENP-A with other autoantibodies were conducted in one participating centre. Inhibition experiments with either the CENP-A peptide or recombinant CENP-B were carried out to analyse the specificity of anti-CENP-A and -B antibodies.ResultsThe CENP-A ELISA results were in good agreement with other ACA detection methods. According to the kappa method, the qualitative agreements were: 0.73 (vs. IIF), 0.81 (vs. LIA), 0.86 (vs. CENP-B ELISA) and 0.97 (vs. EliA® CENP). The quantitative comparison between CENP-A and CENP-B ELISA using 265 samples revealed a correlation value of rho = 0.5 (by Spearman equation). The receiver operating characteristic analysis indicated that the discrimination between SSc patients (n = 131) and various controls (n = 134) was significantly better using the CENP-A as compared to CENP-B ELISA (P < 0.0001). Modified Rodnan skin score was significantly lower in the CENP-A negative group compared to the positive patients (P = 0.013). Inhibition experiments revealed no significant cross reactivity of anti-CENP-A and anti-CENP-B antibodies. Statistically relevant differences for gender ratio (P = 0.0103), specific joint involvement (Jaccoud) (P = 0.0006) and anti-phospholipid syndrome (P = 0.0157) between ACA positive SLE patients and the entire SLE cohort were observed.ConclusionsAnti-CENP-A antibodies as determined by peptide ELISA represent a sensitive, specific and independent marker for the detection of ACA and are useful biomarkers for the diagnosis of SSc. Our data suggest that anti-CENP-A antibodies are a more specific biomarker for SSc than antibodies to CENP-B. Furthers studies are required to verify these findings.

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Section: Discussionmentioning

confidence: 99%

Clinical and serological evaluation of a novel CENP-A peptide based ELISA

Mähler

Maes²,

Blockmans³

et al. 2010

Arthritis Res Ther

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“…Studies have shown that 3% to 17% of patients with PBC also have features of scleroderma, most commonly of the CREST variant [42]. Tojo et al [43] described a subgroup of PBC patients who had associated CREST symptoms and a better prognosis than patients with PBC alone [43]. These patients develop AMA and ACA, with no crossreactivity between the two autoantibodies [44].…”

Section: Antimitochondrial Antibodiesmentioning

confidence: 99%

Antibodies in scleroderma: Direct pathogenicity and phenotypic associations

Chung

Utz²

2004

Curr Rheumatol Rep

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Scleroderma is an autoimmune disease involving endothelial cell damage and fibroblast overproduction of extracellular matrix. Several autoantibodies present in the sera of patients with scleroderma, including anti-endothelial cell, antifibroblast, anti-matrix metalloproteinase, and antifibrillin-1 antibodies, may directly contribute to disease pathogenesis. Scleroderma also is characterized by the presence of antinuclear and antinucleolar antibodies, which correlate with particular phenotypes. These include antitopoisomerase-I, anticentromere, antihistone, anti-polymyositis/scleroderma, anti-Th/To, anti-U3-small nucleolar ribonucleoprotein particle, anti-U1-small nuclear ribonucleoprotein particle, anti-RNA polymerase, and anti-B23 antibodies. Other antibodies classically associated with other autoimmune diseases, such as antiphospholipid, antineutrophil cytoplasmic, and antimitochondrial antibodies, also have been described in patients with scleroderma. This review will summarize the various autoantibodies associated with scleroderma, their putative pathogenic roles, and their phenotypic correlations.

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“…Advanced age, hyperbilirubinemia, low serum albumin and stage 4 (cirrhosis) liver biopsy indicate worse prognosis [1,2]. Nevertheless, survival of patients with PBC and CREST syndrome seems to be better than that of patients with PBC alone [19].…”

Section: Discussionmentioning

confidence: 99%

A Case of Reynolds Syndrome: Scleroderma and Primary Biliary Cirrhosis Overlap Syndrome

Simões

2011

J Med Cases

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Primary biliary cirrhosis (PBC) is a chronic liver condition characterized by bile duct destruction, probably caused by a yet unknown immunological mechanism. Its association with several other autoimmune diseases has been described. The association of the limited cutaneous form of systemic scleroderma (lcSSc) and PBC is known as Reynolds syndrome. The authors describe a case of a 76 year old male patient with Raynaud's phenomenon complaints in 1999. The physical examination revealed sclerodactyly, cutaneous calcifi cations, digital ulcers and facial telangiectasias. Chest radiography showed signs of lung fi brosis. Dilated capillary loop were found in nailfold capillaroscopy. The autoimmunity pattern was compatible with limited systemic sclerosis (antinuclear and anticentromere antibodies were positive). In 2005 the autoimmunity pattern changed, with positive antimitochondrial antibodies. The patient presented with fatigue, pruritus and dyspnea on exertion complaints. Liver function tests showed elevation of alkaline phosphatase and gamma-glutamyl transpeptidase. Although the patient refused liver biopsy, PBC diagnosis was established. In 2008 the patient was admitted to the hospital with anorexia, dyspepsia, ascites, abdominal pain and weight loss. Endoscopy showed esophageal varices and abdominal computed tomography revealed cirrhotic liver. The patient died in 2009 with acute myocardial infarction.

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Clinicolaboratory characteristics of patients with primary biliary cirrhosis associated with CREST symptoms

Cited by 35 publications

References 24 publications

Clinical and serological evaluation of a novel CENP-A peptide based ELISA

Clinical and serological evaluation of a novel CENP-A peptide based ELISA

Antibodies in scleroderma: Direct pathogenicity and phenotypic associations

A Case of Reynolds Syndrome: Scleroderma and Primary Biliary Cirrhosis Overlap Syndrome

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