Detection of IgM and IgG antibodies against SARS-CoV-2 in patients with autoimmune diseases
Authors: Jialin Teng, Jin Dai, Yutong Su, Zhuochao Zhou, Huihui Chi, Liyan Wan, Jianfen Meng, Zhihong Wang, Fan Wang, Yuning Ma, Qiongyi Hu, Xiaobing Cheng, Honglei Liu, Junna Ye, Hui Shi, Yue Sun, Chengde Yang, Xuefeng Wang
Journal: The Lancet Rheumatology (2020)

In December, 2019, an outbreak of the novel coronavirus (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) occurred in Wuhan, China,1Huang C Wang Y Li X et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; 395: 497-506Summary Full Text Full Text PDF PubMed Scopus (33099) Google Scholar and soon spread all over the world. Rapid and accurate diagnosis of SARS-CoV-2 infection is the cornerstone of all efforts to stem its advancement. Molecular detection via RT-PCR can result in falsely negative results due to the low viral loads in a sample. Serological methods are being developed and have proven to be a useful supplementary approach in confirming SARS-CoV-2 infection.2Zhang W Du RH Li B et al.Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes.Emerg Microbes Infect. 2020; 9: 386-389Crossref PubMed Scopus (1326) Google Scholar The US Food and Drug Administration has issued numerous Emergency Use Authorisations, including serological tests; however, the potential for cross-reactivity with antibodies present in the sera of patients with other diseases remains largely unknown. Cross-reactivity of antibodies against SARS-CoV-2 with antibodies against other coronaviruses, such as SARS-CoV, has been shown.3Zhou P Yang XL Wang XG et al.A pneumonia outbreak associated with a new coronavirus of probable bat origin.Nature. 2020; 579: 270-273Crossref PubMed Scopus (14526) Google Scholar In addition, cross-reactivity has been observed from autoantibodies in serum samples from patients with autoimmune disease when testing for SARS-CoV,4Wang Y Sun S Shen H et al.Cross-reaction of SARS-CoV antigen with autoantibodies in autoimmune diseases.Cell Mol Immunol. 2004; 1: 304-307PubMed Google Scholar which shares high sequence identity with SARS-CoV-2. As such, we wanted to determine whether autoantibodies interfere with detection of SARS-CoV-2 antibodies. We collected 290 serum samples from patients with autoimmune disease in our serum library, consisting of 98 patients with rheumatoid arthritis, 100 patients with systemic lupus erythematosus, and 92 patients with Sjogren's syndrome. The samples were collected from Jan 1, 2016, to June 30, 2019, which predates the COVID-19 pandemic. Written informed consent was obtained from all patients. The serological test for SARS-CoV-2 IgM and IgG monoclonal antibodies was done with colloidal gold-labelled kits supplied by Innovita Biotechnology Co, Tangshan, China. The nitrocellulose filter of these colloidal gold-labelled assays are coated with two antigens of SARS-CoV-2 (N protein and S protein). The overall testing sensitivity was 89% (352/397) and specificity was 91% (116/128). Our results showed that both IgG and IgM antibodies against SARS-CoV-2 were not detected in the serum of patients with autoimmune disease, indicating that there was no cross-reactivity between autoantibodies and SARS-CoV-2 antibodies (table). It should be noted, however, that these sera were only analysed using one kit and other kits with different test operating characteristics might produce different results.TableClinical characteristics and auto-antibody profile of patientsRheumatoid arthritis (n=98)SLE (n=100)Sjogren's syndrome (n=92)Men17 (17%)10 (10%)8 (9%)Women81 (83%)90 (90%)84 (91%)Age, years52·3 (13·4)40·1 (15·2)42·6 (12·4)Anti-nuclear antibody positive35 (36%)100 (100%)92 (100%)Anti-dsDNA positive063 (63%)11 (12%)Anti-Smith antibody positive022 (22%)2 (2%)Anti-Sjogren's syndrome antigen positive3 (3%)48 (48%)58 (63%)Anti-SSB positive08 (8%)26 (28%)Anti-U1RNP positive034 (34%)7 (8%)Anti-Rib-P positive014 (14%)4 (4%)Anti-phospholipid antibodies023 (23%)3 (3·3%)Rheumatoid factor47 (48%)14 (14%)21 (23%)Anti-CCP51 (52%)3 (3%)1 (1%)Data are n (%) or mean (SD). SLE=systemic lupus erythematosus. dsDNA=double-stranded DNA. SSB= Sjogren's B. U1RNP=U1 ribonucleoprotein. Rib-P=ribosome P protein. CCP=cyclic citrullinated peptide. Open table in a new tab Data are n (%) or mean (SD). SLE=systemic lupus erythematosus. dsDNA=double-stranded DNA. SSB= Sjogren's B. U1RNP=U1 ribonucleoprotein. Rib-P=ribosome P protein. CCP=cyclic citrullinated peptide. In conclusion, the serological test we assessed showed no cross-reactivity with autoantibodies present in patients with autoimmune disease. Asymptomatic carriers could spread SARS-CoV-2,5Rothe C Schunk M Sothmann P et al.Transmission of 2019-nCoV infection from an asymptomatic contact in Germany.N Engl J Med. 2020; 382: 970-971Crossref PubMed Scopus (2825) Google Scholar and this type of test could make large scale screening of asymptomatic SARS-CoV-2 carriers possible. We propose that serological testing of IgM and IgG antibodies, along with RT-PCR, in clinical practice should help provide an accurate COVID-19 diagnosis, including in patients with autoimmune disease. We declare no competing interests. We appreciate all the participants and students who took part in this study. This research was not funded. Patients consent for publication was not required. Ethics approval was provided by Institutional Research Ethics Committee of Ruijin Hospital (number 2016-62), Shanghai, China. No additional data are available. SARS-CoV-2 serological cross-reactivity with autoantibodiesIn their report on the detection of IgM and IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with autoimmune diseases, Teng and colleagues1 found that the serological test that they assessed showed no cross-reactivity with autoantibodies present in patients with autoimmune disease. However, several potential confounding factors should be considered when assessing the study findings. Hypogammaglobulinaemia (reduced serum immunoglobulin concentrations) might result in false negative antibody test results; therefore, quantitative serum immunoglobulin measurements should be used to interpret SARS-CoV-2 serology results, along with knowledge of any patient history of immunodeficiencies. Full-Text PDF SARS-CoV-2 serological cross-reactivity with autoantibodies – Authors' replyWe thank Kay Weng Choy for the interest in our work and we agree that the results of the chemical assays should consider endogenous compounds. However, performance analysis of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological assay that we used in our experiment showed that icterus and lipaemia were minimally affected, but false positive results can occur as a result of severe haemolysis.1 However, there was no positive result in our test; therefore, there was no haemolysis in our specimens. Full-Text PDF