Objective. A prospective study was performed comparing conventional radiography, 3-phase bone scintigraphy, ultrasound, and magnetic resonance imaging (MRI) with precontrast and dynamic postcon-trast examinations in 60 patients with various forms of arthritis including rheumatoid arthritis (RA), spondyl-arthropathy, and arthritis associated with connective tissue disease. Methods. A total of 840 finger joints were examined clinically and by all 4 imaging methods. Experienced investigators blinded to the clinical findings and diagnoses analyzed all methods independently of each other. The patients were divided into 2 groups. Group 1 included 32 patients (448 finger joints) without radio-logic signs of destructive arthritis (Larsen grades 0-1) of the evaluated hand and wrist and group 2 included 28 patients (392 finger joints) with radiographs revealing erosions (Larsen grade 2) of the evaluated hand and/or wrist. Results. Clinical evaluation, scintigraphy, MRI, and ultrasound were each more sensitive than conventional radiography in detecting inflammatory soft tissue lesions as well as destructive joint processes in arthritis patients in group 1. All differences were statistically significant. We found ultrasound to be even more sensitive than MRI in the detection of synovitis. MRI detected erosions in 92 finger joints (20%; 26 patients) in group 1 that had not been detected by conventional radiography. Conclusion. Our data indicate that MRI and ultrasound are valuable diagnostic methods in patients with arthritis who have normal findings on radiologic evaluation.

Objective. To introduce a new standardized ultrasound score based on 7 joints of the clinically dominant hand and foot (German US7 score) implemented in daily rheumatologic practice. Methods. The ultrasound score included the following joints of the clinically dominant hand and foot: wrist, second and third metacarpophalangeal and proximal interphalangeal, and second and fifth metatarsophalangeal joints. Synovitis and synovial/tenosynovial vascularity were scored semiquantitatively (grade 0 -3) by gray-scale (GS) and power Doppler (PD) ultrasound. Tenosynovitis and erosions were scored for presence. The scoring range was 0 -27 for GS synovitis, 0 -39 for PD synovitis, 0 -7 for GS tenosynovitis, 0 -21 for PD tenosynovitis, and 0 -14 for erosions. Patients with arthritis were examined at baseline and after the start or change of disease-modifying antirheumatic drug (DMARD) and/or tumor necrosis factor ␣ (TNF␣) inhibitor therapy 3 and 6 months later. C-reactive protein level, erythrocyte sedimentation rate, rheumatoid factor, anti-cyclic citrullinated peptide, Disease Activity Score in 28 joints (DAS28), and radiographs of the hands and feet were performed. Results. One hundred twenty patients (76% women) with rheumatoid arthritis (91%) and psoriatic arthritis (9%) were enrolled. In 52 cases (43%), erosions were seen in radiography at baseline. Patients received DMARDs (41%), DMARDs plus TNF␣ inhibitors (41%), or TNF␣ inhibitor monotherapy (18%). At baseline, the mean DAS28 was 5.0 and the synovitis scores were 8.1 in GS ultrasound and 3.3 in PD ultrasound. After 6 months of therapy, the DAS28 significantly decreased to 3.6 (⌬ ‫؍‬ 1.4), and the GS and PD ultrasound scores significantly decreased to 5.5 (؊32%) and 2.0 (؊39%), respectively. Conclusion. The German US7 score is a viable tool for examining patients with arthritis in daily rheumatologic practice because it significantly reflects therapeutic response.

Objective. Modification of antigens represents a trigger for the generation of autoantibodies. In the pathogenesis of rheumatoid arthritis (RA), citrullination of proteins has been shown to be a critical process, and the determination of antibodies against citrullinated antigens has been a diagnostic milestone. We undertook this study to determine whether antibodies to mutated and citrullinated vimentin (MCV) could serve as a diagnostic and prognostic marker for RA.Methods. We identified novel isoforms of human MCV in the synovial fluid of RA patients. The significance of these disease-related modifications was investigated by the analysis of autoantibody reactivities. In a group of 1,151 RA patients, the diagnostic significance and the prognostic value of an anti-MCV enzyme-linked immunosorbent assay (ELISA) were compared with that of an anti-cyclic citrullinated peptide (anti-CCP) ELISA.Results. In RA, sensitivities of 82% and 72% were calculated for the anti-MCV and anti-CCP assays, respectively. The specificity of both assays was comparable (98% and 96%, respectively). In followup analyses of 16 RA patients with moderate disease activity (mean Disease Activity Score in 28 joints [DAS28] of 2.72) and 26 RA patients with active disease (mean DAS28 of 5.07), disease stratification of RA was possible using the anti-MCV assay (P ‫؍‬ 0.0084). A significant correlation of anti-MCV antibodies with the DAS28 was documented (r ‫؍‬ 0.5334, P ‫؍‬ 0.0003), in 42 RA patients (n ‫؍‬ 427 antibody determinations at different time points).

Objective. Analysis of peripheral B cell subsets in patients with systemic lupus erythematosus (SLE) has provided evidence of specific alterations, such as an expansion of CD27؉؉ plasma cells/blasts and transitional B cells. However, memory B cells in lupus have not been thoroughly investigated, and only recently a CD27؊ memory B cell subset was identified in the peripheral blood of lupus patients. Focusing on CD27؊ B cells, this study aimed to identify abnormalities in peripheral B cell subsets in patients with SLE.Methods. Three independent cohorts of lupus patients were used to characterize CD27؊ memory B cells, using multiparameter flow cytometry and singlecell reverse transcription-polymerase chain reaction of heavy-chain transcripts.Results. We identified a homogeneous subset of CD27؊,IgD؊,CD95؉ memory B cells with an activated phenotype that was increased in patients with disease flares and that correlated with disease activity and serologic abnormalities. In contrast, the entire subset of CD27؊,IgD؊ B cells was found to be heterogeneous, did not correlate significantly with lupus activity, and was also increased in patients with bacterial infections. Conclusion. We conclude that CD95 is a useful marker to identify CD27؊ memory B cells with an activated phenotype, which might serve as a biomarker for lupus activity and as a target of further investigations aiming to elucidate the pathogenic potential of these cells and the mechanisms involved in the generation as well as regulation of this CD27؊,IgD؊,CD95؉ memory B cell subset.B cell monitoring has been extensively used recently to assess the effect of B cell-depleting or B cell-modulating therapies and the reconstitution of the peripheral blood B cell repertoire after treatment with B cell-depleting drugs. Expression of CD27 has been particularly useful to discriminate B cell subsets. Although CD27 was originally thought to distinguish between memory B cells and plasma cells and between memory B cells and naive B cells (1,2), more recently the heterogeneity of CD27Ϫ B cells has become apparent. The contribution of transitional B cells to this subpopulation has been shown to be high in some patients with systemic lupus erythematosus (SLE) (3). In this regard, after B cell depletion, immature and transitional B cells dominate the peripheral blood for months (4). Conversely, a recent analysis of B cell subsets in patients with Sjögren's syndrome demonstrated a predominance of CD27Ϫ B cells, of which ϳ10% were B cells with

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Objective. Anti-citrullinated protein antibodies (ACPA) exhibit unique specificity for rheumatoid arthritis. However, it is incompletely understood whether and how ACPA contribute to disease pathogenesis. The Fc part of human IgG carries 2 N-linked glycan moieties that are crucial for the structural stability of the antibody and that modulate both its binding affinity to Fc␥ receptors and its ability to activate complement. We undertook this study to analyze Fc glycosylation of IgG1 ACPA in serum and synovial fluid (SF) in order to further characterize the immune response to citrullinated antigens.Methods. ACPA were isolated by affinity purification using cyclic citrullinated peptides as antigen. IgG1 Fc glycosylation was analyzed by mass spectrometry. ACPA IgG1 glycan profiles were compared with glycan profiles of total serum IgG1 obtained from 85 wellcharacterized patients. Glycan profiles of paired SF and serum samples were available from 11 additional patients.Results. Compared with the pool of serum IgG1, ACPA IgG1 lacked terminal sialic acid residues. In SF, ACPA were highly agalactosylated and lacked sialic acid residues, a feature that was not detected for total SF IgG1. Moreover, differential ACPA glycan profiles were detected in rheumatoid factor (RF)-positive and RFnegative patients.Conclusion. ACPA IgG1 exhibit a specific Fclinked glycan profile that is distinct from that of total serum IgG1. Moreover, Fc glycosylation of ACPA differs markedly between SF and serum. Since Fc glycosylation directly affects the recruitment of Fc-mediated effector mechanisms, these data could further our understanding of the contribution of ACPA to disease pathogenesis.Antibodies relevant to tissue pathology in autoimmune diseases are identified based on antigen-binding specificity of the variable region. Only very few autoantibodies, however, mediate pathology by direct interaction with the antigen. In most other cases, the constant region (Fc part) determines antibody-mediated effector functions, such as complement activation, antibodydependent cell-mediated cytotoxicity (ADCC), and engagement of activating or inhibitory Fc receptors (FcR). These Fc-mediated effects are influenced by the amino acid sequence of the Fc part (i.e., antibody isotype and subclass) and by Fc-linked carbohydrate structures. The latter are located in the C␥2 domain of the heavy chain in close proximity to amino acids that interact with FcR and the complement system. Accordingly, Fc-linked carbohydrate structures have recently received increasing attention, since modification of Fc-linked glycan residues of therapeutic antibodies has been shown to strongly influence the therapeutic potential of the antibodies (1-6).

The SmD1 protein is a specific target for the autoantibody response in SLE. To further analyze this reactivity epitope, mapping was performed with cellulose-bound 13-mer peptides overlapping 10 amino acids (aa). In this initial approach, 4 out of 15 SLE sera recognized more than five overlapping peptides of the SmD1 C-terminus. Therefore, longer oligopeptides of up to 37 aa of this region were generated and probed for as antigens by ELISA. For the SmD1 aa 83-119 polypeptide, there was a striking increase of reactivity with 70.0% positive reactions out of 167 SLE sera. In contrast, 105 healthy control sera were negative, and only 8.3% of sera from patients with other inflammatory diseases ( n ϭ 267) exhibited a response, which was of low level only.

A greater reduction in radiographic progression after initial combination therapy with ADA and MTX was seen at week 48, even after discontinuation of ADA treatment at week 24. This sustained effect was not found at the primary endpoint (DAS28 reduction).