Autoantibodies to the 27 C-terminal amino acids of calpastatin are detected in a restricted set of connective tissue diseases and may be useful for diagnosis of rheumatoid arthritis in community cases of very early arthritis.
BACKGROUND
Calpastatin is the natural inhibitor of calpains, a protease that is overexpressed in rheumatoid synovial tissue and plays a key role in cartilage destruction. Autoantibodies to calpastatin (ACAST) were recently detected in rheumatoid arthritis (RA). Our aim was to determine their prevalence and their clinical significance.


METHODS
ACAST were detected in a solid-phase enzyme-linked immunosorbent assay (ELISA) using a synthetic peptide corresponding to the 27 C-terminal amino acids of calpastatin (CAST-C27) as the antigen. All sera reacting with this peptide also bound to purified erythrocyte calpastatin in an ELISA and/or an immunoblot assay. The frequencies and clinical significance of ACAST-C27 were assessed in sera from a well-documented population of 102 community-recruited patients (76 females; mean age 50 yr) with RA that had been evolving for <5 yr (median 2 yr) (group 1), 109 healthy blood donors, 289 patients with non-RA rheumatic disease and 88 community cases of very early (median 4 months) arthritis, i.e. 58 RA and 30 non-RA patients (group 2).


RESULTS
The sensitivity of ACAST-C27 for RA was 19.5% (20/102) in group 1 and 10.3% (6/58) in group 2. These antibodies were also found in patients with anti-double-stranded DNA-positive systemic lupus erythematosus (SLE) (15.5%) and patients with anti-Ro-positive Sjögren's syndrome (18.5%). However, they were not detected in cases of rheumatism resembling early RA, i.e. peripheral spondylarthropathies. ACAST-C27 were not detected in the 30 non-RA patients of group 2. They were predominantly of immunoglobulin isotype G3 and exclusively expressed lambda chains. Among ACAST-C27-positive sera, eight out of 20 (group 1) and four out of six (group 2) were negative for rheumatoid factor and anti-keratin antibodies/antiperinuclear factor. No relationship was found between ACAST-C27 and clinical, biological or radiological findings.


CONCLUSIONS
ACAST-C27 are detected only in a restricted set of connective tissue diseases and therefore appear to be specific for RA when antibodies that are usually associated with SLE or primary Sjögren's syndrome are negative. Because of their presence in community cases of very early RA, particularly in some seronegative forms, ACAST-C27 may be useful in discriminating recent-onset RA from the more common non-RA rheumatic diseases, such as spondylarthropathies.
Vittecoq
O
O
Unité INSERM 519 et Institut Fédératif de Recherche Multidisciplinaire sur les Peptides (IFRMP 23), Faculté de Médecine et de Pharmacie, Rouen, France.
Salle
V
V
Jouen-Beades
F
F
Krzanowska
K
K
Ménard
J F
JF
Gayet
A
A
Fardellone
P
P
Tauveron
P
P
Le Loët
X
X
Tron
F
F
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000918:Antibody Specificity; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000276:immunology*; D003240:Connective Tissue Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007147:Immunoglobulin Light Chains / Q000276:immunology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011446:Prospective Studies; D017434:Protein Structure, Tertiary; D011859:Radiography; D012680:Sensitivity and Specificity; D016036:Seroepidemiologic Studies
D001323:Autoantibodies; D002135:Calcium-Binding Proteins; D007074:Immunoglobulin G; D007147:Immunoglobulin Light Chains; C033668:calpastatin