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Systemic lupus erythematosus with anti-centromere antibodies: An infrequent finding without scleroderma related features
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ARTICLE IN PRESS Med Clin (Barc). 2016;xxx(xx):xxx–xxx
www.elsevier.es/medicinaclinica
Scientific letter
Systemic lupus erythematosus with anti-centromere antibodies: An infrequent finding without scleroderma related features夽 Lupus eritematoso sistémico con anticuerpos anticentrómero: un hallazgo infrecuente sin características de esclerodermia Dear Editor, The anti-centromere antibodies in patients with scleroderma (SSc) are significantly associated with Raynaud’s phenomenon, sclerodactyly, arthralgia, telangiectasis, pulmonary hypertension and severe peripheral ischemia with finger ulcers and necrosis.1 They are very specific to limited SSc, with a prevalence of between 40 and 80%.1 These autoantibodies are also present, although to a lesser extent, in diffuse SSc (3–12%), primary biliary cirrhosis (PBC) and primary Raynaud.2 Detection of anti-centromere antibodies in patients with primary Raynaud could be important in the early diagnosis of SSc, since patients may develop the said disease. However, the anti-centromere antibodies primarily associated with the aforementioned diseases have been detected in other systemic autoimmune connective tissue conditions, such as Sjögren’s syndrome (SS)3 and systemic lupus erythematosus (SLE),4 although their clinical significance in these connective tissue conditions is so far unknown. The anti-centromere antibodies in patients with SLE are considered rare autoantibodies; with an incidence of between 0.925 and 5.6%.6 Due to its low frequency in patients with SLE, there is little information in relation to whether these autoantibodies are associated with a different subset within SLE. The possible existence of differences in SLE patients regarding the presence or absence of anti-centromere antibodies is analyzed in this paper, in a case–control study. A retrospective case–control study was conducted, in which a total of 102 patients with SLE diagnosed in the Rheumatology Service of the Hospital de Jerez de la Frontera (north of the province of Cadiz area) over the past 10 years were included (2005–2015). All patients included had the diagnostic criteria of the American College of Rheumatology (ACR, “American College of Rheumatology”) of 1997; the new criteria proposed by the Systemic Lupus International Collaborating Clinics (SLICC) 20127 were considered for this study. 6 cases of SLE with anti-centromere antibodies, 4 women and 2 men were included, with a mean age ± SD of 55.00 ± 2.90 years. The control group consisted of 96 patients without anticentromere antibodies, 84 women and 12 men with an average age of 44.72 ± 14.38 years. There were no significant differences in the age and sex of both groups (cases and controls) (p > 0.05).
夽 Please cite this article as: Cabrera CM. Lupus eritematoso sistémico con anticuerpos anticentrómero: un hallazgo infrecuente sin características de esclerodermia. Med Clin (Barc). 2016. http://dx.doi.org/10.1016/j.medcli.2015.12.008
The determination of antinuclear antibodies was performed by indirect immunofluorescence on HEp-2 cells (Biosystems SA, Barcelona, Spain). Only samples with titers ≥1/160 were considered as a positive result. Positive serum samples were studied by immunoblot with the ANA Profile 5 EUROLINE kit (EUROIMMUN AG, Luebeck, Germany) to determine the reactivity to extractable nuclear antigens (ENA) (RNP, Sm, SS-A, SS-B, CENP-B, P-ribosomal, Ku and PCNA). The values of the following parameters were quantified by chemiluminescence using a Zenit RA analyser (Menarini Diagnostics, Barcelona, Spain): anti-double-stranded DNA antibodies (reference values: 0–50 IU/ml), anti-cardiolipin IgG antibodies (reference values: 0–20 GPL), anti-cardiolipin IgM antibodies (reference values: 0–10 MPL), anti-beta2-glycoprotein I IgG antibodies (reference values: 0–20 GPL) and anti-beta2-glycoprotein I IgM antibodies (reference values: 0–10 MPL). The concentrations of the C3 and C4 complement factors were determined by Immunonephelometry using a BN II analyser (Siemens Healthcare Diagnostics, Marburg, Germany) (reference values: 90–180 and 10–40 mg/dl for C3 and C4, respectively). The nonparametric Mann–Whitney U test was used in the statistical analysis of quantitative variables. Chi-square with the Fisher exact test was used for qualitative variables. The study was performed using the SPSS statistical program® version 15.0, and p values <0.05 were considered significant results. All patients with anti-centromere antibodies (n = 6) had SLE diagnostic clinical manifestations (ACR and SLICC criteria); however, three patients exhibited Raynaud’s phenomenon (Table 1). Hypocomplementemia was considered with a decrease in C3 or C4, according to the new 2012 diagnostic criteria (SLICC).7 Similarly, levels of antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies and anti-beta2-glycoprotein I) were among these new criteria, which were also determined in this study (Table 1). In 5 of the 6 cases of SLE (83.33%), anti-centromere antibodies were associated with anti-ENA autoantibodies (anti-RNP, anti-Sm, anti-SS-A, anti-SS-B and anti-ribosomal P), and antidouble stranded DNA (anti-DNA) (Table 1). When comparing clinical and laboratory characteristics between the two groups of patients it was found that SLE patients with anti-centromere antibodies were diagnosed later in life compared to controls (5133 ± 13.09 vs 37.89 ± 13.63 years of age, respectively; p = 0.035). The remaining clinical variables were not significantly different. However, in the study of laboratory variables, an increased frequency of anti-Sm antibodies was observed in cases of SLE with anti-centromere antibodies (4/6; 66.67%) compared to controls (23/96; 23, 95%) (p = 0.041). The clinical significance of the presence of anti-centromere antibodies in connective tissue diseases other than SSc or SSc overlap syndromes is, to date, controversial. Within the SSc/overlap syndrome these antibodies are associated with a higher limited SSc prevalence and a reduced disease severity.1 Anti-centromere antibody titers are generally stable over time and are not associated with clinical activity.1 Similarly, anti-centromere antibodies in SSc
˜ S.L.U. All rights reserved. 2387-0206/© 2015 Elsevier Espana,
MEDCLE-3489; No. of Pages 3
G Model 2
ARTICLE IN PRESS Scientific letter / Med Clin (Barc). 2016;xxx(xx):xxx–xxx
Table 1 Clinical and laboratory characteristics of cases and controls of systemic lupus erythematosus. Variable
Cases (n = 6)
Controls (n = 96)
p
Clinical variables Age at diagnosis in years Arthritis/arthralgia Raynaud’s phenomenon Acute Cutaneous Lupus Canker sores Photosensitivity Alopecia Lupus nephritis Antiphospholipid syndrome Secondary Sjögren’s syndrome Serositis (pleuritis/pericarditis) Hematologic manifestations Neurological manifestations
51.33 ± 13.09 6 (100) 3 (50) 1 (16.67) 2 (33.33) 1 (16.67) 0 1 (16.67) 1 (16.67) 0 0 0 1 (16.67)
37.89 ± 13.63 68 (70.83) 29 (30.20) 46 (47.91) 28 (29.16) 19 (19.79) 23 (23.95) 23 (23.95) 22 (22.91) 13 (13.54) 9 (9.37) 13 (13.54) 8 (8.33)
0.035* ns ns ns ns ns ns ns ns ns ns ns ns
Laboratory variables Hypocomplementemia Lupus anticoagulant Cardiolipin antibodies (IgG and/or IgM) Anti-B2GI antibodies (IgG and/or IgM) Anti-Sm Anti-RNP Anti-SS-A Anti-SS-B Anti-ribosomal P Anti-Ku Anti-PCNA Anti-DNA
4 (66.67) 0 1 (16.67) 3 (50) 4 (66.67) 4 (66.67) 2 (33.33) 1 (16.67) 2 (33.33) 0 0 2 (33.33)
40 (41.67) 16 (16.67) 19 (19.79) 26 (27.08) 23 (23.95) 27 (28.12) 42 (43.75) 17 (17.70) 7 (7.29) 1 (1.04) 5 (5.21) 37 (38.54)
ns ns ns ns 0.041* 0.068 ns ns 0.087 ns ns ns
Anti-DNA: anti-deoxyribonucleic acid antibodies; anti-B2GI: anti-beta2-glycoprotein I; anti-PCNA: antinuclear antibody of proliferating cells; anti-RNP: antiribonucleoprotein antibodies; SD: standard deviation; ns: not statistically significant differences. Data are expressed as mean ± SD or n (%). * p < 0.05.
usually appear alone, i.e. as the only autoantibodies.2 However, in other connective tissue diseases such as SS, rheumatoid arthritis (RA) or SLE, anti-centromere antibodies appear more often together with other autoantibodies both, against ENA as well as against double-stranded DNA (anti-DNA).2 In these other connective tissue diseases (SS, RA and SLE), the most common clinical manifestations associated with SSc are Raynaud’s followed by telangiectasis.2 The incidence of anti-centromere antibodies in SLE patients is very low.4 A frequency of 1.9% was described for these autoantibodies in the only study conducted in patients with SLE published to date among Spanish population.8 In this paper, Respaldiza et al.8 does not find any difference between clinical and immunological manifestations in a group of SLE patients with anti-centromere antibodies (11 patients) compared to a control group (274 patients), although they do not include age at the time of diagnosis as a variable. However, this study of 6 cases and 96 controls shows that anti-centromere antibodies appear in SLE patients diagnosed at a later age. This finding, however, is consistent with that described by Nakano et al.6 in a Japanese population with SLE. Similarly, these authors found that among patients with SLE and anti-centromere antibodies Raynaud’s phenomenon was more frequent when compared to the control group.6 Within the SSc classification criteria (ACR/EULAR 2013),9 the presence of Raynaud’s phenomenon and anti-centromere antibodies have a score of 3 points, respectively. A value higher than or equal to 9 points is required for the diagnosis of SSc.9 3 study patients (Table 1) had the joint presence of one clinical criterion (Raynaud’s phenomenon) and one laboratory criterion (anti-centromere antibodies) for SSc, which was not sufficient for the diagnosis of SLE/SSc overlap syndrome. Only one patient had a SLE/PBC overlap syndrome (data not shown). In the medical literature SLE/SSc overlap syndromes are very rare; a high frequency of anti-DNA antibodies and anti-Scl70 has been found within them.10 The anti-centromere antibodies in patients with SLE/SSc only represent 10.5%.10
An increased frequency of anti-Sm antibodies compared to the control group (4/6 vs 23/96, p = 0.041) was further found in this study. And in line with previous studies,2,5,8 anti-centromere antibodies in 5 of the 6 cases studied appeared associated with other autoantibodies (anti-ENA and anti-DNA). Therefore, after considering the results of this study, it cannot be said that the presence of anti-centromere antibodies in SLE patients among the Spanish population is associated with a subset of this disease, as there have been no significant differences with regard to SSc-related clinical manifestations. However, these autoantibodies are more common in people who develop symptoms of SLE later on in life, and with a higher frequency of anti-Sm antibodies.
References 1. Hamagushi Y. Autoantibody profiles in systemic sclerosis: predictive value for clinical evaluation and prognosis. J Dermatol. 2010;37:42–53. 2. Miyawaki S, Asanuma H, Nishiyama S, Yoshinaga Y. Clinical and serological heterogeneity in patients with anticentromere antibodies. J Rheumatol. 2005;32:1488–94. 3. Bournia VK, Diamanti KD, Vlachoyiannopoulos PG, Moutsopoulos HM. Anticentromere antibody positive Sjögren’s syndrome: a retrospective descriptive analysis. Arthritis Res Ther. 2010;12:R47. 4. Russo K, Hoch S, Dima C, Varga J, Teodorescu M. Circulating anticentromere CENP-A and CENP-B antibodies in patients with diffuse and limited systemic sclerosis, systemic lupus erythematosus, and rheumatoid arthritis. J Rheumatol. 2000;27:142–8. 5. Fredi M, Cavazzana I, Quinzanini M, Taraborelli M, Cartella S, Tincani A, et al. Rare autoantibodies to cellular antigens in systemic lupus erythematosus. Lupus. 2014;23:672–7. 6. Nakano M, Ohuchi Y, Hasegawa H, Kuroda T, Ito S, Gejyo F. Clinical significance of anticentromere antibodies in patients with systemic lupus erythematosus. J Rheumatol. 2000;27:1403–7. 7. Petri M, Orbai AM, Alarcón GS, Gordon C, Merrill JT, Fortin PR, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64:2677–86. ˜ C, Garcia-Hernandez FJ, Castillo MJ, Magarino ˜ 8. Respaldiza N, Wichmann I, Ocana MI, et al. Anti-centromere antibodies in patients with systemic lupus erythematosus. Scand J Rheumatol. 2006;35:290–4.
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ARTICLE IN PRESS Scientific letter / Med Clin (Barc). 2016;xxx(xx):xxx–xxx
9. Valentini G, Marcoccia A, Cuomo G, Iudici M, Vettori S. The concept of early systemic sclerosis following 2013 ACR/EULAR criteria for the classification of systemic sclerosis. Curr Rheumatol Rev. 2014;10:38–44. 10. Pakozdi A, Nihtyanova S, Moinzadeh P, Ong VH, Black CM, Denton CP. Clinical and serological hallmarks of systemic overlap syndromes. J Rheumatol. 2011;38:2406–9.
Carmen M. Cabrera Sección de Inmunología, Servicio de Hematología, Hospital de Jerez de la Frontera, Jerez de la Frontera, Cádiz, Spain E-mail address: [email protected]
3
ARTICLE IN PRESS Med Clin (Barc). 2016;xxx(xx):xxx–xxx
www.elsevier.es/medicinaclinica
Scientific letter
Systemic lupus erythematosus with anti-centromere antibodies: An infrequent finding without scleroderma related features夽 Lupus eritematoso sistémico con anticuerpos anticentrómero: un hallazgo infrecuente sin características de esclerodermia Dear Editor, The anti-centromere antibodies in patients with scleroderma (SSc) are significantly associated with Raynaud’s phenomenon, sclerodactyly, arthralgia, telangiectasis, pulmonary hypertension and severe peripheral ischemia with finger ulcers and necrosis.1 They are very specific to limited SSc, with a prevalence of between 40 and 80%.1 These autoantibodies are also present, although to a lesser extent, in diffuse SSc (3–12%), primary biliary cirrhosis (PBC) and primary Raynaud.2 Detection of anti-centromere antibodies in patients with primary Raynaud could be important in the early diagnosis of SSc, since patients may develop the said disease. However, the anti-centromere antibodies primarily associated with the aforementioned diseases have been detected in other systemic autoimmune connective tissue conditions, such as Sjögren’s syndrome (SS)3 and systemic lupus erythematosus (SLE),4 although their clinical significance in these connective tissue conditions is so far unknown. The anti-centromere antibodies in patients with SLE are considered rare autoantibodies; with an incidence of between 0.925 and 5.6%.6 Due to its low frequency in patients with SLE, there is little information in relation to whether these autoantibodies are associated with a different subset within SLE. The possible existence of differences in SLE patients regarding the presence or absence of anti-centromere antibodies is analyzed in this paper, in a case–control study. A retrospective case–control study was conducted, in which a total of 102 patients with SLE diagnosed in the Rheumatology Service of the Hospital de Jerez de la Frontera (north of the province of Cadiz area) over the past 10 years were included (2005–2015). All patients included had the diagnostic criteria of the American College of Rheumatology (ACR, “American College of Rheumatology”) of 1997; the new criteria proposed by the Systemic Lupus International Collaborating Clinics (SLICC) 20127 were considered for this study. 6 cases of SLE with anti-centromere antibodies, 4 women and 2 men were included, with a mean age ± SD of 55.00 ± 2.90 years. The control group consisted of 96 patients without anticentromere antibodies, 84 women and 12 men with an average age of 44.72 ± 14.38 years. There were no significant differences in the age and sex of both groups (cases and controls) (p > 0.05).
夽 Please cite this article as: Cabrera CM. Lupus eritematoso sistémico con anticuerpos anticentrómero: un hallazgo infrecuente sin características de esclerodermia. Med Clin (Barc). 2016. http://dx.doi.org/10.1016/j.medcli.2015.12.008
The determination of antinuclear antibodies was performed by indirect immunofluorescence on HEp-2 cells (Biosystems SA, Barcelona, Spain). Only samples with titers ≥1/160 were considered as a positive result. Positive serum samples were studied by immunoblot with the ANA Profile 5 EUROLINE kit (EUROIMMUN AG, Luebeck, Germany) to determine the reactivity to extractable nuclear antigens (ENA) (RNP, Sm, SS-A, SS-B, CENP-B, P-ribosomal, Ku and PCNA). The values of the following parameters were quantified by chemiluminescence using a Zenit RA analyser (Menarini Diagnostics, Barcelona, Spain): anti-double-stranded DNA antibodies (reference values: 0–50 IU/ml), anti-cardiolipin IgG antibodies (reference values: 0–20 GPL), anti-cardiolipin IgM antibodies (reference values: 0–10 MPL), anti-beta2-glycoprotein I IgG antibodies (reference values: 0–20 GPL) and anti-beta2-glycoprotein I IgM antibodies (reference values: 0–10 MPL). The concentrations of the C3 and C4 complement factors were determined by Immunonephelometry using a BN II analyser (Siemens Healthcare Diagnostics, Marburg, Germany) (reference values: 90–180 and 10–40 mg/dl for C3 and C4, respectively). The nonparametric Mann–Whitney U test was used in the statistical analysis of quantitative variables. Chi-square with the Fisher exact test was used for qualitative variables. The study was performed using the SPSS statistical program® version 15.0, and p values <0.05 were considered significant results. All patients with anti-centromere antibodies (n = 6) had SLE diagnostic clinical manifestations (ACR and SLICC criteria); however, three patients exhibited Raynaud’s phenomenon (Table 1). Hypocomplementemia was considered with a decrease in C3 or C4, according to the new 2012 diagnostic criteria (SLICC).7 Similarly, levels of antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies and anti-beta2-glycoprotein I) were among these new criteria, which were also determined in this study (Table 1). In 5 of the 6 cases of SLE (83.33%), anti-centromere antibodies were associated with anti-ENA autoantibodies (anti-RNP, anti-Sm, anti-SS-A, anti-SS-B and anti-ribosomal P), and antidouble stranded DNA (anti-DNA) (Table 1). When comparing clinical and laboratory characteristics between the two groups of patients it was found that SLE patients with anti-centromere antibodies were diagnosed later in life compared to controls (5133 ± 13.09 vs 37.89 ± 13.63 years of age, respectively; p = 0.035). The remaining clinical variables were not significantly different. However, in the study of laboratory variables, an increased frequency of anti-Sm antibodies was observed in cases of SLE with anti-centromere antibodies (4/6; 66.67%) compared to controls (23/96; 23, 95%) (p = 0.041). The clinical significance of the presence of anti-centromere antibodies in connective tissue diseases other than SSc or SSc overlap syndromes is, to date, controversial. Within the SSc/overlap syndrome these antibodies are associated with a higher limited SSc prevalence and a reduced disease severity.1 Anti-centromere antibody titers are generally stable over time and are not associated with clinical activity.1 Similarly, anti-centromere antibodies in SSc
˜ S.L.U. All rights reserved. 2387-0206/© 2015 Elsevier Espana,
MEDCLE-3489; No. of Pages 3
G Model 2
ARTICLE IN PRESS Scientific letter / Med Clin (Barc). 2016;xxx(xx):xxx–xxx
Table 1 Clinical and laboratory characteristics of cases and controls of systemic lupus erythematosus. Variable
Cases (n = 6)
Controls (n = 96)
p
Clinical variables Age at diagnosis in years Arthritis/arthralgia Raynaud’s phenomenon Acute Cutaneous Lupus Canker sores Photosensitivity Alopecia Lupus nephritis Antiphospholipid syndrome Secondary Sjögren’s syndrome Serositis (pleuritis/pericarditis) Hematologic manifestations Neurological manifestations
51.33 ± 13.09 6 (100) 3 (50) 1 (16.67) 2 (33.33) 1 (16.67) 0 1 (16.67) 1 (16.67) 0 0 0 1 (16.67)
37.89 ± 13.63 68 (70.83) 29 (30.20) 46 (47.91) 28 (29.16) 19 (19.79) 23 (23.95) 23 (23.95) 22 (22.91) 13 (13.54) 9 (9.37) 13 (13.54) 8 (8.33)
0.035* ns ns ns ns ns ns ns ns ns ns ns ns
Laboratory variables Hypocomplementemia Lupus anticoagulant Cardiolipin antibodies (IgG and/or IgM) Anti-B2GI antibodies (IgG and/or IgM) Anti-Sm Anti-RNP Anti-SS-A Anti-SS-B Anti-ribosomal P Anti-Ku Anti-PCNA Anti-DNA
4 (66.67) 0 1 (16.67) 3 (50) 4 (66.67) 4 (66.67) 2 (33.33) 1 (16.67) 2 (33.33) 0 0 2 (33.33)
40 (41.67) 16 (16.67) 19 (19.79) 26 (27.08) 23 (23.95) 27 (28.12) 42 (43.75) 17 (17.70) 7 (7.29) 1 (1.04) 5 (5.21) 37 (38.54)
ns ns ns ns 0.041* 0.068 ns ns 0.087 ns ns ns
Anti-DNA: anti-deoxyribonucleic acid antibodies; anti-B2GI: anti-beta2-glycoprotein I; anti-PCNA: antinuclear antibody of proliferating cells; anti-RNP: antiribonucleoprotein antibodies; SD: standard deviation; ns: not statistically significant differences. Data are expressed as mean ± SD or n (%). * p < 0.05.
usually appear alone, i.e. as the only autoantibodies.2 However, in other connective tissue diseases such as SS, rheumatoid arthritis (RA) or SLE, anti-centromere antibodies appear more often together with other autoantibodies both, against ENA as well as against double-stranded DNA (anti-DNA).2 In these other connective tissue diseases (SS, RA and SLE), the most common clinical manifestations associated with SSc are Raynaud’s followed by telangiectasis.2 The incidence of anti-centromere antibodies in SLE patients is very low.4 A frequency of 1.9% was described for these autoantibodies in the only study conducted in patients with SLE published to date among Spanish population.8 In this paper, Respaldiza et al.8 does not find any difference between clinical and immunological manifestations in a group of SLE patients with anti-centromere antibodies (11 patients) compared to a control group (274 patients), although they do not include age at the time of diagnosis as a variable. However, this study of 6 cases and 96 controls shows that anti-centromere antibodies appear in SLE patients diagnosed at a later age. This finding, however, is consistent with that described by Nakano et al.6 in a Japanese population with SLE. Similarly, these authors found that among patients with SLE and anti-centromere antibodies Raynaud’s phenomenon was more frequent when compared to the control group.6 Within the SSc classification criteria (ACR/EULAR 2013),9 the presence of Raynaud’s phenomenon and anti-centromere antibodies have a score of 3 points, respectively. A value higher than or equal to 9 points is required for the diagnosis of SSc.9 3 study patients (Table 1) had the joint presence of one clinical criterion (Raynaud’s phenomenon) and one laboratory criterion (anti-centromere antibodies) for SSc, which was not sufficient for the diagnosis of SLE/SSc overlap syndrome. Only one patient had a SLE/PBC overlap syndrome (data not shown). In the medical literature SLE/SSc overlap syndromes are very rare; a high frequency of anti-DNA antibodies and anti-Scl70 has been found within them.10 The anti-centromere antibodies in patients with SLE/SSc only represent 10.5%.10
An increased frequency of anti-Sm antibodies compared to the control group (4/6 vs 23/96, p = 0.041) was further found in this study. And in line with previous studies,2,5,8 anti-centromere antibodies in 5 of the 6 cases studied appeared associated with other autoantibodies (anti-ENA and anti-DNA). Therefore, after considering the results of this study, it cannot be said that the presence of anti-centromere antibodies in SLE patients among the Spanish population is associated with a subset of this disease, as there have been no significant differences with regard to SSc-related clinical manifestations. However, these autoantibodies are more common in people who develop symptoms of SLE later on in life, and with a higher frequency of anti-Sm antibodies.
References 1. Hamagushi Y. Autoantibody profiles in systemic sclerosis: predictive value for clinical evaluation and prognosis. J Dermatol. 2010;37:42–53. 2. Miyawaki S, Asanuma H, Nishiyama S, Yoshinaga Y. Clinical and serological heterogeneity in patients with anticentromere antibodies. J Rheumatol. 2005;32:1488–94. 3. Bournia VK, Diamanti KD, Vlachoyiannopoulos PG, Moutsopoulos HM. Anticentromere antibody positive Sjögren’s syndrome: a retrospective descriptive analysis. Arthritis Res Ther. 2010;12:R47. 4. Russo K, Hoch S, Dima C, Varga J, Teodorescu M. Circulating anticentromere CENP-A and CENP-B antibodies in patients with diffuse and limited systemic sclerosis, systemic lupus erythematosus, and rheumatoid arthritis. J Rheumatol. 2000;27:142–8. 5. Fredi M, Cavazzana I, Quinzanini M, Taraborelli M, Cartella S, Tincani A, et al. Rare autoantibodies to cellular antigens in systemic lupus erythematosus. Lupus. 2014;23:672–7. 6. Nakano M, Ohuchi Y, Hasegawa H, Kuroda T, Ito S, Gejyo F. Clinical significance of anticentromere antibodies in patients with systemic lupus erythematosus. J Rheumatol. 2000;27:1403–7. 7. Petri M, Orbai AM, Alarcón GS, Gordon C, Merrill JT, Fortin PR, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64:2677–86. ˜ C, Garcia-Hernandez FJ, Castillo MJ, Magarino ˜ 8. Respaldiza N, Wichmann I, Ocana MI, et al. Anti-centromere antibodies in patients with systemic lupus erythematosus. Scand J Rheumatol. 2006;35:290–4.
G Model
ARTICLE IN PRESS Scientific letter / Med Clin (Barc). 2016;xxx(xx):xxx–xxx
9. Valentini G, Marcoccia A, Cuomo G, Iudici M, Vettori S. The concept of early systemic sclerosis following 2013 ACR/EULAR criteria for the classification of systemic sclerosis. Curr Rheumatol Rev. 2014;10:38–44. 10. Pakozdi A, Nihtyanova S, Moinzadeh P, Ong VH, Black CM, Denton CP. Clinical and serological hallmarks of systemic overlap syndromes. J Rheumatol. 2011;38:2406–9.
Carmen M. Cabrera Sección de Inmunología, Servicio de Hematología, Hospital de Jerez de la Frontera, Jerez de la Frontera, Cádiz, Spain E-mail address: [email protected]
3