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Objectives: Autoantibodies from the sera of Sjögren's syndrome patients (SS IgG) have been suggested to inhibit muscarinic receptor function. However, the acute nature of such an inhibitory effect remains controversial. In this study, we investigated the acute effects of SS IgG on muscarinic receptor function in human submandibular gland (HSG) cells., Methods: The effects of autoantibodies on muscarinic receptor function were studied using microspectrofluorimetry, whole-cell patch clamp, immunofluorescence confocal microscopy, and a co-immunoprecipitation assay., Results: Carbachol (CCh) was found to consistently increase intracellular calcium concentration ([Ca(2+) ](i) ) and activate K(+) current in HSG cells. However, pretreatment of the cells with SS IgG for 5 or 30 min significantly attenuated these responses, with a substantially more prominent effect after 30 min of treatment. Like CCh, adenosine 5'-triphosphate (ATP) also increased [Ca(2+) ](i) and activated K(+) currents in HSG cells, although pretreatment with SS IgG did not affect the cellular response to ATP. CCh was found to reorganize α-fodrin in HSG cells in a Ca(2+) -dependent manner. However, pretreatment with SS IgG prevented the cytoskeletal reorganization of α-fodrin induced by CCh., Conclusions: SS IgG acutely and reversibly inhibited muscarinic receptor function, thereby inhibiting the Ca(2+) mobilization necessary for the activation of K(+) currents and α-fodrin reorganization in HSG cells., (© 2011 John Wiley & Sons A/S.)

Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease, characterized by chronic, erosive polyarthritis and by the presence of various autoantibodies in serum and synovial fluid. Since rheumatoid factor (RF) was first described, a number of other autoantibodies have been discovered in RA patients. The autoantigens recognized by these autoantibodies include cartilage components, chaperones, enzymes, nuclear proteins and citrullinated proteins. However, the clinical significances and pathogenic roles of these antibodies are largely unknown except for RF and anticitrullinated protein antibodies (ACPAs), whose clinical usefulness has been acknowledged due to their acceptable sensitivities and specificities, and prognostic values. This review presents and discusses the current state of the art regarding RF and ACPA in RA.

Objectives: Recently, autoantibodies directed against muscarinic type 3 receptor (M3R) have been reported in patients with primary SS. However, the precise epitope(s) of the M3R that interacts with SS autoantibodies remains unclear. The aim of this study was to identify the functional epitope of M3R which interacts with SS immunoglobulin G (IgG)., Methods: Purified IgGs were obtained from the sera of seven SS patients (six primary and one secondary SS) and two normal persons. We examined whether SS IgG inhibits M3R function and identified the epitope using six synthetic peptides covering all the extracellular domains of M3R by microspectrofluorimetry and surface plasmon resonance-based optical biosensor system (BIAcore system)., Results: A volume of 0.5 mg/ml SS IgG inhibited carbachol (CCh)-induced [Ca(2+)](i) transient (CICT) in human submandibular gland (HSG) cells. However, co-incubation of SS IgG with the 6th peptide (514-527 amino acid region) corresponding to the third extracellular loop of M3R, recovered CICT. The result was further confirmed by BIAcore analysis. We found that the 6th peptide interacts with IgGs from three primary SS patients in a concentration-dependent manner. The synthetic peptide which consists of amino acids 228-237 corresponding to the COOH-terminus of the second extracellular loop of M3R also bound to SS IgG. However, normal IgGs did not interact with the 6th peptide., Conclusions: The results suggest that the third extracellular loop of M3R represents a functional epitope bound by SS IgG, and thereby partly inhibits M3R function.

The objective of this study is to evaluate the association between anti-neuronal antibody (anti-NA) and central nervous system (CNS) manifestations of systemic lupus erythematosus (SLE) and other rheumatic diseases using a flow cytometric method. Anti-NA was measured by flow cytometry in serum and cerebrospinal fluid (CSF) samples from patients with SLE (n=44 for serum, n=17 for CSF), other rheumatic diseases (n=64 for serum, n=21 for CSF) and from healthy controls (n=65 for serum, n=18 for CSF). Serum anti-NA was more frequently observed in SLE (31.8%, 14/44) than in other rheumatic diseases (4.7%, 3/64, P<0.001) or in healthy controls (0%, 0/65, P<0.00001). In SLE patients, the frequency of serum anti-NA was significantly higher in CNS-SLE (76.5%, 13/17) than in non CNS-SLE (3.7%, 1/27, P<0.000001). CSF anti-NA was detected in 88.2% (15/17) of CNS-SLE and was more frequently detected in CNS-SLE (15/17, 88.2%) than in other rheumatic diseases with CNS involvement (1/21, 4.8%, P<0.000001) or in healthy controls (0/18, P<0.000001). In conclusion, serum anti-NA was more frequently found in CNS-SLE than in non CNS-SLE, other rheumatic diseases or in healthy controls. The frequency of CSF anti-NA in CNS-SLE was significantly higher than in other rheumatic diseases with CNS involvement or in healthy controls.

Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease, characterized by chronic, erosive polyarthritis and by the presence of various autoantibodies in serum and synovial fluid. Since rheumatoid factor (RF) was first described, a number of other autoantibodies have been discovered in RA patients. The autoantigens recognized by these autoantibodies include cartilage components, chaperones, enzymes, nuclear proteins and citrullinated proteins. However, the clinical significances and pathogenic roles of these antibodies are largely unknown except for RF and anticitrullinated protein antibodies (ACPAs), whose clinical usefulness has been acknowledged due to their acceptable sensitivities and specificities, and prognostic values. This review presents and discusses the current state of the art regarding RF and ACPA in RA. [ABSTRACT FROM PUBLISHER]