Date: Sunday, November 5, 2017
Session Title: Sjögren's Syndrome Poster I: Translational Research
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Over the last decades, several post translationally modified proteins have been identified as auto-antigens in rheumatoid arthritis (RA). No data regarding Abs against acetylated proteins (AAPA) and very few on Abs against carbamylated proteins (anti-CarP) are currently available in primary Sjögren’s syndrome (pSS). Acetylation of lysine/ornithin results from the addition of an acetyl group by the N-acetyltranferase enzyme, while carbamylation is the conversion of lysine residues into homocitrulline. In RA, carbamylation can be induced by cigarette smoke. The aim of our study was to investigate the prevalence and significance of AAPA and anti-CarP Abs in pSS.
Eighty-seven pSS patients according to the 2002 American-European Consensus Criteria where enrolled. AAPA and anti-CarP were assessed by ELISA using mutated vimentin acetylated or carbamylated in position 7 as antigen. Acetylation could target either a lysin or an ornithin residue. To assess the possible effect of nearby antigens, acetylation and carbamylation were also alternatively included in position 2 (inverse peptide). Acetylated histone and non histone peptides were also employed as antigens. Clinical and serological records, including glandular and extraglandular manifestations, cardiovascular (CV) risk factors and CV events were retrospectively collected.
AAPA were identified in 20 pSS patients (23%). Seven patients displayed only one AAPA specificity while 13 displayed 2 or more AAPA specificities. Anti-CarP Abs have been identified in 4 pSS patients (5%) and in all cases the antigen was mutated vimentin carbamylated at position 7 but not the inverse peptide. AAPA+ patients did not display extra-glandular involvement including renal, pulmonary, gastrointestinal, central/peripheral nervous system manifestations or myositis. Conversely, binary logistic regression revealed that AAPA positivity was associated with cardiac (namely pericarditis) and cardiovascular (CV) events (heart failure, pulmonary arterial hypertension, pulmonary embolism) (odds ratio=11; p<0.0001) but not with smoking or systemic arterial hypertension. pSS patients with anti-CarP Abs displayed more frequently leukopenia (p=0.01) and parotid gland swelling (p=0.03) but surprisingly none of the anti-CarP+ patients displayed articular involvement and none of them was a current or former smoker.
Our study demonstrated for the first time that AAPA are detectable in pSS. Although preliminary, our results support the evidence of a possible association of AAPA and cardiac/CV manifestations. Likewise, specific anti-CarP Abs against mutated carbamylated vimentin are present in a small proportion of pSS patients and seem to be associated with leukopenia and parotid gland swelling but not with articular involvement and smoking. These results are of particular importance in light of the increased CV risk in pSS and will be assessed in a larger cohort of patients fopr validation purposes. Furthermore, it might be speculated that carbamylation in pSS may be induced by mechanisms other than cigarette smoking.
To cite this abstract in AMA style:Alunno A, Carubbi F, Bang H, Bistoni O, Studenic P, Steiner G, Bartoloni E, Smolen JS, Gerli R. Anti-Modified Protein Antibody Response Pattern in Primary Sjögren’s Syndrome: Clinical and Prognostic Implications [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/anti-modified-protein-antibody-response-pattern-in-primary-sjogrens-syndrome-clinical-and-prognostic-implications/. Accessed September 20, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-modified-protein-antibody-response-pattern-in-primary-sjogrens-syndrome-clinical-and-prognostic-implications/