Anti-centromere antibody exhibits specific distribution levels among anti-nuclear antibodies and may characterize a distinct subset in rheumatoid arthritis

Kuramoto, Nobuyuki; Ohmura, Koichiro; Ikari, Katsunori; Yano, Koichiro; Furu, Moritoshi; Yamakawa, Naoyuki; Hashimoto, Motomu; Ito, Hiromu; Fujii, Tomoyuki; Murakami, Kosaku; Nakashima, Ran; Imura, Yoshitaka; Yukawa, Naoichiro; Yoshifuji, Hajime; Taniguchi, Atsuo; Momohara, Shigeki; Yamanaka, Hisashi; Matsuda, Fumihiko; Mimori, Tsuneyo; Terao, Chikashi

doi:10.1038/s41598-017-07137-4

Cited by 8 publications

(3 citation statements)

References 26 publications

(26 reference statements)

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“…ANA tests can be falsely positive in HIV [6]. Anti-dsDNA antibodies, anticentromere antibodies, and antihistone antibodies are overall highly specific for systemic lupus erythematosus, limited cutaneous systemic sclerosis, and drug-induced lupus, respectively [7, 8, 9]. However, this patient did not manifest any other signs of those autoimmune conditions.…”

Section: Discussionmentioning

confidence: 99%

Perforating Peripheral Ulcerative Keratitis in Syphilis

Ploysangam¹,

Mattern²

2019

Case Rep Ophthalmol

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PurposeTo present a case of peripheral ulcerative keratitis with perforation in the setting of syphilis.MethodA single observational case report in urban USA.Case PresentationA patient with multiple sexual partners presented with bilateral peripheral ulcerative keratitis, unilateral corneal perforation, and a pustular rash. Workup was positive for syphilis as well as HSV, HIV, and multiple autoantibody tests. Findings improved after treatment for syphilis.ConclusionBilateral peripheral ulcerative keratitis in syphilis has been reported in one prior case. However, corneal perforation in the setting of syphilis infection has not, to our knowledge, been reported previously.

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Section: Discussionmentioning

confidence: 99%

Perforating Peripheral Ulcerative Keratitis in Syphilis

Ploysangam¹,

Mattern²

2019

Case Rep Ophthalmol

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“…However, ACA are not specific to SSc. Although with reduced frequency, ACA are detected in multiple additional autoimmune pathologies and malignancies, including primary Sjögren syndrome, 3 systemic lupus erythematosus, 4 rheumatoid arthritis, 5 type 1 diabetes mellitus 6 and breast cancer without symptoms of rheumatologic disease 7 . Subsequent reports identified ACA autoantigens.…”

Section: Introductionmentioning

confidence: 99%

The peptide link between pathogens and human centromere proteins

Huang¹,

Liang²,

Liu³

2022

Scand J Immunol

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Anti-centromere antibodies (ACA) were firstly detected in 1980 via indirect immunofluorescence (IIF) after incubation of human epithelial cell line 2 (HEp-2) cell substrates with serum samples from individuals with CREST (calcinosis, Raynaud phenomenon, oesophageal dysmotility, sclerodactyly and telangiectasias) syndrome. 1 Then, ACA were shown to be useful molecular markers for diagnosing systemic sclerosis (SSc), with a positive rate approximating 20%-40%. 2 However, ACA are not specific to SSc. Although with reduced frequency, ACA are detected in multiple additional autoimmune pathologies and malignancies, including primary Sjögren syndrome, 3 systemic lupus erythematosus, 4 rheumatoid arthritis, 5 type 1 diabetes mellitus 6 and breast cancer without symptoms of rheumatologic disease. 7 Subsequent reports identified ACA autoantigens. Currently, many centromere proteins (CENPs) are considered ACA autoantigens, with CENP-A, CENP-B and CENP-C being major centromere proteins. 8 The above three autoantigens with similar structures represent the best-described centromere constituents in humans.Centromere proteins are considered intracellular, nuclear proteins contributing to the assembly of kinetochores that are critical to mitosis progression and chromosome segregation. CENP-A represents a 17-kDa protein found at centromeric sites with high sequence similarity to histone H3. 9 Meanwhile, CENP-B (80 kDa) interacts with αsatellite DNA sequences 10 at the heterochromatic centromere. CENP-C represents a 140-kD protein found in the kinetochore's inner plate. 11 ACA detection in serum samples from individuals with SSc or other pathologies suggests CENPs may cause the immune system to induce autoimmune reactions. However, multiple unanswered questions and data gaps remain. First, how antibodies are primed to CENPs is unclear. As nuclear proteins, CENPs are theoretically inaccessible to the immune system.

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“…[8] в подавляющем большинстве случаев АЦА ассоциировались исследователями с лимитированной формой ССД [9,10]. Вместе с тем, помимо лимитированной формы ССД, АЦА встречаются при БШ [11], ПБЦ [12], СКВ [7], РА [13,14], изолированном феномене Рейно [7], изолированной дигитальной гангрене [15][16][17], некоторых опухолях [7]. Более того, по данным ряда исследований с длительным наблюдением за АЦА-позитивными пациентами, серопозитивность по АЦА вовсе не гарантирует наличие какого-либо заболевания [18,19].…”

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CLINICAL AND LABORATORY FEATURES OF ANTICENTROMERE ANTIBODY-POSITIVE SJö GREN’S SYNDROME

Чальцев¹,

Васильев²,

Palshina³

et al. 2019

Naučno-praktičeskaâ revmatologiâ

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Objective: to study the clinical and laboratory features of patients with anticentromere antibody (ACA) positive Sjö gren’s syndrome (SjS); to assess the spectrum of autoantibodies in patients of this group; to determine the frequency with which the SjS patients who are highly positive for ACA, meet the international classification criteria for SjS and systemic sclerosis (SS); to reveal the incidence of MALT lymphomas in this patient group; to estimate the incidence of primary biliary cirrhosis (PBC)/biliary lesions as part of autoimmune epithelitis in SjS in this patient group.Material and methods. A total of 83 patients with ACA positive SjS were comprehensively examined at the V.A. Nasonova Research Institute of Rheumatology during the period 2012 to 2018. The inclusion criteria were con formity to the 2001 Russian SjS criteria and a high ACA level. MALT lymphomas were diagnosed on the basis of histological and immunohistochemical studies and polymerase chain reaction-based determination of B-cell clonality in the biopsy samples of affected organs according to the World Health Organization classification of Hematopoietic Tumors. The diagnosis of PBC/biliary lesions was made on the basis of histological and immunohistochemical studies of liver biopsy specimens.Results and discussion. The investigation revealed low detection rates for anti-Ro antibodies (32.5%), anti-La antibodies (7.2%) and rheumatoid factor (RF) (21.7%), which were typical for the classical SjS immunophenotype), increased ESR (14%), leukopenia (7%), hypergammaglobulinemia (17.6%), elevated levels of IgG (9.5%) and IgA (18.7%), and hypocomplementemia (16.1%) in the ACA positive SjS patients. Despite the low detection rate of RF, 15 (18%) patients in this group developed MALT lymphomas: 14 patients had salivary gland MALT lymphoma and one patient had tonsil MALT lymphoma with peripheral lymph node involvement (generalized marginal zone lymphoma). Also, the patients of this group showed high detection rates for AMA antibodies (34.6%), increased IgM level (29.7%) and a higher risk for PBC/biliary lesions as a manifestation of autoimmune epithelitis in SjS (14.5%). AMA-antibodies were absent in only two patients who were diagnosed with liver disease according to biopsy specimens. Nervous system and renal lesions, antiphospholipid syndrome, rheumatoid arthritis, hypergammaglobulinemic purpura, and cryoglobulinemic vasculitis were much less common and sporadic. Also ACA-positive SjS patients often have Raynaud’s phenomenon (54.9%) with scleroderma-type capillaroscopic changes (68%) and a limited form of SS (24%) according to the 2013 ACR criteria.Conclusion. ACA-positive SjS is a subtype of the disease, which is significantly different from the classic one in a number of clinical and laboratory signs and characterized by an increased risk for SS, MALT lymphomas, and PBC/biliary lesions as a manifestation of autoimmune epithelitis in SjS which in some cases leads to the underdiagnosis of SjS. ACA should be considered as pathogenetically related to SjS autoantibodies; and all patients who are seropositive for ACA should be examined for SjS and PBC/biliary lesions as a manifestation of autoimmune epithelitis in SjS regardless of whether they have SS or not, as well as complaints of dry mouth and eyes. Patients with significantly enlarged salivary glands should undergo biopsy to rule out or confirm MALT lymphoma before initiating hormonal, antilymphoproliferative, and anti-B-cell therapy.

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Anti-centromere antibody exhibits specific distribution levels among anti-nuclear antibodies and may characterize a distinct subset in rheumatoid arthritis

Cited by 8 publications

References 26 publications

Perforating Peripheral Ulcerative Keratitis in Syphilis

Perforating Peripheral Ulcerative Keratitis in Syphilis

The peptide link between pathogens and human centromere proteins

CLINICAL AND LABORATORY FEATURES OF ANTICENTROMERE ANTIBODY-POSITIVE SJö GREN’S SYNDROME

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