Fine specificity of the Ro/SSA autoantibody response in relation to serological and clinical findings in 96 patients with self-reported cutaneous symptoms induced by the sun

Abstract

Anti-Ro/SSA assays assist the clinician in distinguishing autoimmune diseases such as Sjögrenś syndrome (SS), systemic lupus erythematosus (SLE) and subacute cutaneous lupus erythematosus (SCLE). The objective of the study was to investigate the fine specificity of the autoantibodies in relation to clinical presentation as well as environmental and endogenous factors such as photosensitivity, smoking and immunoglobulin (Ig) levels in patients with Ro/SSA autoantibodies. Serum samples from 96 anti-Ro/SSA positive photosensitive patients were tested for autoantibody levels by enzyme-linked immunosorbent assay (ELISA) using purified recombinant Ro52 kd, Ro60 kd and La proteins as antigens. The highest levels of anti-Ro52 and anti-La were observed in patients with primary SS, and the lowest levels of anti-Ro52 in chronic cutaneous lupus erythematosus (CCLE). SCLE patients with systemic disease (SLE and/or SS) showed higher levels of anti-Ro52 than SCLE limited to the skin. A correlation between high serum levels of IgG and anti-Ro52 (P < 0.01) and between IgA and anti-Ro52 (P < 0.05) and anti-Ro60 (P < 0.05) was found. Polymorphic light eruption (PLE) was common in all diagnostic groups but did not correlate with autoantibody levels. Smoking was more common in lupus patients than in SS patients. Our findings thus propose different mechanisms for different clinical presentations of Ro/SSA positive patients. The testing of anti-Ro52 antibodies might serve as a prognostic tool in photosensitive cutaneous diseases.

Keywords

autoimmunity cigarette smoking Ro/SSA Sjögren's syndrome subacute cutaneous lupus erythematosus

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References

Sontheimer RD , Maddison PJ , Reichlin M , Jordon RE , Stastny P , Gilliam JN . Serologic and HLA associations in subacute cutaneous lupus erythematosus, a clinical subset of lupus erythematosus . Ann Intern Med 1982; 97: 664–671 .

Provost TT , Levin LS , Watson RM , Mayo M , Ratrie H 3rd. Detection of anti-Ro(SSA) antibodies by gel double diffusion and a ‘sandwich’ ELISA in systemic and subacute cutaneous lupus erythematosus and Sjogren's syndrome . J Autoimmun 1991; 4: 87–96 .

Simmons-O'Brien E , Chen S , Watson R et al. One hundred anti-Ro (SS-A) antibody positive patients: a 10-year follow-up . Medicine (Baltimore) 1995; 74: 109–130 .

LeFeber WP , Norris DA , Ryan SR et al. Ultraviolet light induces binding of antibodies to selected nuclear antigens on cultured human keratinocytes . J Clin Invest 1984; 74: 1545–1551 .

Furukawa F , Kashihara-Sawami M , Lyons MB , Norris DA . Binding of antibodies to the extractable nuclear antigens SS-A/Ro and SS-B/La is induced on the surface of human keratinocytes by ultraviolet light (UVL): implications for the pathogenesis of photosensitive cutaneous lupus . J Invest Dermatol 1990; 94: 77–85 .

Furukawa F , Itoh T , Wakita H et al. Keratinocytes from patients with lupus erythematosus show enhanced cytotoxicity to ultraviolet radiation and to antibody-mediated cytotoxicity . Clin Exp Immunol 1999; 118: 164–170 .

Criswell LA , Merlino LA , Cerhan JR et al. Cigarette smoking and the risk of rheumatoid arthritis among postmenopausal women: results from the Iowa Women's Health Study . Am J Med 2002; 112: 465–471 .

Costenbader KH , Kim DJ , Peerzada J et al. Cigarette smoking and the risk of systemic lupus erythematosus: a meta-analysis . Arthritis Rheum 2004; 50: 849–857 .

Boeckler P , Milea M , Meyer A et al. The combination of complement deficiency and cigarette smoking as risk factor for cutaneous lupus erythematosus in men; a focus on combined C2/C4 deficiency . Br J Dermatol 2005; 152: 265–270 .

10.

Tengner P , Halse AK , Haga HJ , Jonsson R , Wahren-Herlenius M . Detection of anti-Ro/SSA and anti-La/SSB autoantibody-producing cells in salivary glands from patients with Sjogren's syndrome . Arthritis Rheum 1998; 41: 2238–2248 .

11.

Salomonsson S , Wahren-Herlenius M . Local production of Ro/SSA and La/SSB autoantibodies in the target organ coincides with high levels of circulating antibodies in sera of patients with Sjogren's syndrome . Scand J Rheumatol 2003; 32: 79–82 .

12.

Tan EM , Cohen AS , Fries JF et al. The 1982 revised criteria for the classification of systemic lupus erythematosus . Arthritis Rheum 1982; 25: 1271–1277 .

13.

Albrecht J , Berlin JA , Braverman IM et al. Dermatology position paper on the revision of the 1982 ACR criteria for systemic lupus erythematosus . Lupus 2004; 13: 839–849 .

14.

Popovic K , Nyberg F , Wahren-Herlenius M , Nyberg F . A serology-based approach combined with clinical examination of 125 Ro/SSA-positive patients to define incidence and prevalence of subacute cutaneous lupus erythematosus . Arthritis Rheum 2007; 56: 255–264 .

15.

Vitali C , Bombardieri S , Jonsson R et al. Classification criteria for Sjogren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group . Ann Rheum Dis 2002; 61: 554–558 .

16.

Arnett FC , Edworthy SM , Bloch DA et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis . Arthritis Rheum 1988; 31: 315–324 .

17.

Mosca M , Neri R , Bombardieri S . Undifferentiated connective tissue diseases (UCTD): a review of the literature and a proposal for preliminary classification criteria . Clin Exp Rheumatol 1999; 17: 615–620 .

18.

Elagib KE , Tengner P , Levi M et al. Immunoglobulin variable genes and epitope recognition of human monoclonal anti-Ro 52-kd in primary Sjogren's syndrome . Arthritis Rheum 1999; 42: 2471–2481 .

19.

Salomonsson S , Jonsson MV , Skarstein K et al. Cellular basis of ectopic germinal center formation and autoantibody production in the target organ of patients with Sjogren's syndrome . Arthritis Rheum 2003; 48: 3187–3201 .

20.

Hassan AB , Lundberg IE , Isenberg D , Wahren-Herlenius M . Serial analysis of Ro/SSA and La/SSB antibody levels and correlation with clinical disease activity in patients with systemic lupus erythematosus . Scand J Rheumatol 2002; 31: 133–139 .

21.

Lee LA , Roberts CM , Frank MB , McCubbin VR , Reichlin M . The autoantibody response to Ro/SSA in cutaneous lupus erythematosus . Arch Dermatol 1994; 130: 1262–1268 .

22.

Peene I , Meheus L , Veys EM , De Keyser F . Diagnostic associations in a large and consecutively identified population positive for anti-SSA and/or anti-SSB: the range of associated diseases differs according to the detailed serotype . Ann Rheum Dis 2002; 61: 1090–1094 .

23.

Miao FJ , Green PG , Benowitz N , Levine JD . Central terminals of nociceptors are targets for nicotine suppression of inflammation . Neuroscience 2004; 123: 777–784 .

24.

Padyukov L , Silva C , Stolt P , Alfredsson L , Klareskog L . A geneenvironment interaction between smoking and shared epitope genes in HLA-DR provides a high risk of seropositive rheumatoid arthritis . Arthritis Rheum 2004; 50: 3085–3092 .

25.

Krug M , Wunsche A , Blum A . [Addiction to tobacco and the consequences for the skin]. Hautarzt 2004; 55: 301–315 ; quiz 316.

26.

Kramer U , Lemmen CH , Behrendt H et al. The effect of environmental tobacco smoke on eczema and allergic sensitization in children . Br J Dermatol 2004; 150: 111–118 .

27.

Naldi L. Cigarette smoking and psoriasis . Clin Dermatol 1998; 16: 571–574 .

28.

Misery L.

Nicotine effects on skin: are they positive or negative?

Exp Dermatol 2004; 13: 665–670 .

29.

Jewell ML , McCauliffe DP . Patients with cutaneous lupus erythematosus who smoke are less responsive to antimalarial treatment . J Am Acad Dermatol 2000; 42: 983-987 .

30.

Hagforsen E , Edvinsson M , Nordlind K , Michaelsson G . Expression of nicotinic receptors in the skin of patients with palmoplantar pustulosis . Br J Dermatol 2002; 146: 383–391 .

31.

Bodeutsch C , de Wilde PC , Kater L et al. Quantitative immunohistologic study of lip biopsies. Evaluation of diagnostic and prognostic value in Sjogren's syndrome . Pathol Res Pract 1992; 188: 599–602 .

32.

Zandbelt MM , Wentink JR , de Wilde PC , van Damme PA , van de Putte LB , van den Hoogen FH . The synergistic value of focus score and IgA% score of sublabial salivary gland biopsy for the accuracy of the diagnosis of Sjogren's syndrome: a 10-year comparison . Rheumatology (Oxford) 2002; 41: 819–823 .

33.

Roguedas AM , Misery L , Sassolas B , Le Masson G , Pennec YL , Youinou P . Cutaneous manifestations of primary Sjogren's syndrome are underestimated . Clin Exp Rheumatol 2004; 22: 632–636 .

34.

Hasan T , Nyberg F , Stephansson E et al. Photosensitivity in lupus erythematosus, UV photoprovocation results compared with history of photosensitivity and clinical findings . Br J Dermatol 1997; 136: 699–705 .

35.

Millard TP , Kondeatis E , Cox A et al. A candidate gene analysis of three related photosensitivity disorders: cutaneous lupus erythematosus, polymorphic light eruption and actinic prurigo . Br J Dermatol 2001; 145: 229–236 .

36.

Ros AM , Wennersten G . Current aspects of polymorphous light eruptions in Sweden . Photodermatol 1986; 3: 298–302 .