A Study On The Relationships Between Auto-antibodies To The Epitopes On SSA/Ro6O And QTc Interval As Well As The Common Clinical Lesions In Associated With Connective Tissue Disease

BackgroudAutoantibody to SSA/Ro, which was one of the most common anti-nuclearantibodies, could be present in many autoimmune diseases, such as systemic lupuserythematosus (SLE), primary systemic sclerosis (pSS), subacute cutaneous lupuserythematosus (SCLE), Sj gren’s syndrome, neonatal lupus erythematosus (NLE)and so on, and might be associated with some clinical manifestations in these diseases,including arrhythmia, rash, photosensitivity, leukopenia, thrombocytopenia,interstitial pneumonia, vasculitis, parotid gland enlargement, glandular lesions,hypergammaglobulinemia and etc. The ribonucleoprotein SSA/Ro was the targetauto-antigen which was consisted of SSA/Ro60and SSA/Ro52proteins.Investigations had demonstrated that Ro60antigen, which was recognized byautoantibody to SSA/Ro60, was comprised of20different epitopes. Each of theepitopes had its own specific autoantibody, which might be related withmiscellaneous clinical manifestations of the autoimmune diseases. It had been widelyaccepted that SSA/Ro60antibodies could be passed from mother to fetus throughplacenta and could result in neonatal heart damages, even the permanent lesions, suchas neonatal P-R interval prolongation, congenital complete atrioventricular block,prolonged corrected QTc interval, and so on. Several studies had demonstrated thatSSA/Ro60antibodies might also produce some damaging effects on adult heart. Forexample, autoantibody to SSA/Ro60in adult patients showed to have markedrelationship with the prolonged corrected QTc interval, which could increase the risk of sudden cardiac death. However, it was still unclear that how the SSA/Ro60antibody lead to the heart injuries, and it was also vague that what relation wasbetween auto-antibodies against the20epitopes on SSA/Ro60antigen and heartdamages.Objectives1. To explore the relationship between auto-antibodies against the20different epitopeson SSA/Ro60and miscellaneous clinical manifestations in the connective tissuediseases (CTDs) with SSA/Ro60autoimmunity.2. To investigate the relations between antibodies to20different epitopes of SSA/Ro60and the heart injurie（sQTc interval on electrocardiogram and pericardial effusion） inassociated CTDs.MethodsSera and clinical datum were collected from150patients with CTDs, including106patients with SLE,14patients with pSS and30patients with undifferentiatedconnective tissue disease (uCTD). All of the selected patients had positive laboratorytest for autoantibody against SSA/Ro60.30healthy controls were also involved inthis study and their sera were collected.20multiple antigenic peptides (MAPs) wereartificially synthesized according to the amino acid sequence of20positive epitopesSSA/Ro60antigen, and1control segment was also synthesized. Enzyme linkedimmunosorbent assay (ELISA) with the21recombinant MAPs as solid phase ligands,was employed to detect anti-MAPs antibodies in150sera from the selected patientswith CTDs and30sera from healthy controls. The relationships between ELISAresults for anti-MAPs antibodies and the clinical manifestations were analyzedstatistically.Resluts1. There were significant differences in the distributions of anti-MAP1and anti-MAP21 antibody in different CTDs.2. There were no obvious relations between any of the20anti-MAPs antibodies andrash or oral ulcer or Raynaud’s phenomenon. By analyzing the results of ELISA, thepatients with salivary gland injury, arthritis, alopecia and peripheral neuropathy hadmore active anti-MAP1, anti-MAP8, anti-MAP5and anti-MAP18antibody,respectively; the patients with lacrimal gland injury had more intensive anti-MAP1and anti-MAP14antibody; the patients with photosensitivity showed more activeanti-MAP7and anti-MAP14antibody.3. Anti-MAP12antibody and anti-MAP14antibody showed correlation with pericardialeffusion. Both of the anti-MAP5antibody and the anti-MAP8antibody had positiveassociation with QTc interval on electrocardiogram.Conclusions1. Auto-antibodies against different epitopes on SSA/Ro60antigen showed differentdistributed spectrum in SLE, pSS and uCTD.2. Autoantibodies to different epitopes on SSA/Ro60antigen were associated withvarious clinical manifestations of CTDs, which might be one of mechanisms for themiscellaneous damages in the associated CTDs.3. The anti-MAP12antibody and the anti-MAP14antibody had an obviously correlationwith pericardial effusion in the CTDs with autoimmunity to SSA/Ro60antigen.4. Both the anti-MAP5antibody and the anti-MAP8antibody had significantly positiveassociation with QTc interval on electrocardiogram. While prolonged QTc intervalmeant higher potential risk of sudden cardiac death, detection of anti-MAP5antibodyand anti-MAP8antibody might be more valuable than detection for anti-SSA/Ro60 antibody to identify and follow up the patients with the potential risk, and to estimatetheir prognosis.