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Longitudinal anti-nuclear antibody (ANA) seroconversion in systemic lupus erythematosus: a prospective study of Swedish cases with recent-onset disease.
Clin Exp Immunol. 2020 03; 199(3):245-254.CE

Abstract

Serum immunoglobulin (Ig)G anti-nuclear antibodies (ANA) detected by indirect immunofluorescence (IF) microscopy remains a hallmark of systemic lupus erythematosus (SLE). Whether or not IF-ANA status varies over time is controversial. We therefore designed a prospective study with longitudinal follow-up of patients with recent-onset SLE. The study population consisted of 54 recently diagnosed SLE cases, all meeting the 1982 American College of Rheumatology (ACR) and/or the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria. Clinical follow-up data, including disease activity, organ damage and sera, were collected from clinical onset of SLE and onwards, in most cases yearly (0-96 months). IF-ANA was analysed on human epithelial cells-2 (HEp-2) cells and categorized regarding staining patterns. Using an addressable laser bead assay (FIDIS™ Connective profile), we measured IgG-ANA fine specificities against Ro52/SSA, Ro60/SSA, Sjögren's syndrome type B antigen (La/SSB), Smith antigen (Sm), Smith antigen/ribonucleoprotein (Sm/RNP), U1 RNP (U1RNP), dsDNA, ribosomal-P protein and histone. At baseline, all patients were judged ANA-positive at an abnormal titre corresponding to the 95th percentile of healthy blood donors, but seven of 54 patients (13%) lost ANA-positivity over time. Homogeneous (AC-1; 46%) and speckled (AC-4 or 5; 31%) were the most frequently observed patterns at inclusion, whereas 7% switched pattern at least once during follow-up. Established associations between ANA fine specificities and clinical data were confirmed. Levels of anti-Sm/RNP, but not of anti-dsDNA, correlated with clinical disease activity [modified SLE disease activity 2000 (mSLEDAI-2K)]. Our data indicate that a considerable proportion of Swedish patients with SLE lose ANA-positivity over time, whereas consistent staining patterns were frequent. The clinical and mechanistic relevance of ANA seroconversion remains uncertain. Further prospective evaluations in larger SLE populations with more diverse ethnicities are warranted.

Authors+Show Affiliations

Rheumatology/Division of Neuro and Inflammation Sciences, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.Rheumatology/Division of Neuro and Inflammation Sciences, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.Clinical Immunology/Division of Neuro and Inflammation Sciences, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.Swedish Institute for Disability Research, Department of Behavioural Sciences and Learning, Linköping University, Linköping, Sweden.Rheumatology/Division of Neuro and Inflammation Sciences, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.Rheumatology/Division of Neuro and Inflammation Sciences, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31778219

Citation

Frodlund, M, et al. "Longitudinal Anti-nuclear Antibody (ANA) Seroconversion in Systemic Lupus Erythematosus: a Prospective Study of Swedish Cases With Recent-onset Disease." Clinical and Experimental Immunology, vol. 199, no. 3, 2020, pp. 245-254.
Frodlund M, Wetterö J, Dahle C, et al. Longitudinal anti-nuclear antibody (ANA) seroconversion in systemic lupus erythematosus: a prospective study of Swedish cases with recent-onset disease. Clin Exp Immunol. 2020;199(3):245-254.
Frodlund, M., Wetterö, J., Dahle, C., Dahlström, Ö., Skogh, T., Rönnelid, J., & Sjöwall, C. (2020). Longitudinal anti-nuclear antibody (ANA) seroconversion in systemic lupus erythematosus: a prospective study of Swedish cases with recent-onset disease. Clinical and Experimental Immunology, 199(3), 245-254. https://doi.org/10.1111/cei.13402
Frodlund M, et al. Longitudinal Anti-nuclear Antibody (ANA) Seroconversion in Systemic Lupus Erythematosus: a Prospective Study of Swedish Cases With Recent-onset Disease. Clin Exp Immunol. 2020;199(3):245-254. PubMed PMID: 31778219.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Longitudinal anti-nuclear antibody (ANA) seroconversion in systemic lupus erythematosus: a prospective study of Swedish cases with recent-onset disease. AU - Frodlund,M, AU - Wetterö,J, AU - Dahle,C, AU - Dahlström,Ö, AU - Skogh,T, AU - Rönnelid,J, AU - Sjöwall,C, Y1 - 2019/12/19/ PY - 2019/11/26/accepted PY - 2021/03/01/pmc-release PY - 2019/11/30/pubmed PY - 2020/7/28/medline PY - 2019/11/29/entrez KW - autoantibodies KW - autoimmunity KW - complement KW - human KW - systemic lupus erythematosus SP - 245 EP - 254 JF - Clinical and experimental immunology JO - Clin. Exp. Immunol. VL - 199 IS - 3 N2 - Serum immunoglobulin (Ig)G anti-nuclear antibodies (ANA) detected by indirect immunofluorescence (IF) microscopy remains a hallmark of systemic lupus erythematosus (SLE). Whether or not IF-ANA status varies over time is controversial. We therefore designed a prospective study with longitudinal follow-up of patients with recent-onset SLE. The study population consisted of 54 recently diagnosed SLE cases, all meeting the 1982 American College of Rheumatology (ACR) and/or the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria. Clinical follow-up data, including disease activity, organ damage and sera, were collected from clinical onset of SLE and onwards, in most cases yearly (0-96 months). IF-ANA was analysed on human epithelial cells-2 (HEp-2) cells and categorized regarding staining patterns. Using an addressable laser bead assay (FIDIS™ Connective profile), we measured IgG-ANA fine specificities against Ro52/SSA, Ro60/SSA, Sjögren's syndrome type B antigen (La/SSB), Smith antigen (Sm), Smith antigen/ribonucleoprotein (Sm/RNP), U1 RNP (U1RNP), dsDNA, ribosomal-P protein and histone. At baseline, all patients were judged ANA-positive at an abnormal titre corresponding to the 95th percentile of healthy blood donors, but seven of 54 patients (13%) lost ANA-positivity over time. Homogeneous (AC-1; 46%) and speckled (AC-4 or 5; 31%) were the most frequently observed patterns at inclusion, whereas 7% switched pattern at least once during follow-up. Established associations between ANA fine specificities and clinical data were confirmed. Levels of anti-Sm/RNP, but not of anti-dsDNA, correlated with clinical disease activity [modified SLE disease activity 2000 (mSLEDAI-2K)]. Our data indicate that a considerable proportion of Swedish patients with SLE lose ANA-positivity over time, whereas consistent staining patterns were frequent. The clinical and mechanistic relevance of ANA seroconversion remains uncertain. Further prospective evaluations in larger SLE populations with more diverse ethnicities are warranted. SN - 1365-2249 UR - https://www.unboundmedicine.com/medline/citation/31778219/Longitudinal_anti_nuclear_antibody__ANA__seroconversion_in_systemic_lupus_erythematosus:_a_prospective_study_of_Swedish_cases_with_recent_onset_disease_ L2 - https://doi.org/10.1111/cei.13402 DB - PRIME DP - Unbound Medicine ER -