OBJECTIVE Recently, new classification criteria for rheumatoid arthritis (RA) have been devised by methodology that used first a quantitative approach (data from databases), then a qualitative... Show moreOBJECTIVE Recently, new classification criteria for rheumatoid arthritis (RA) have been devised by methodology that used first a quantitative approach (data from databases), then a qualitative approach (consensus; based on paper patients), and finally a common sense-based approach (evaluation of the former phases). Now the individual items that make up these criteria are being evaluated. This study was undertaken to analyze the item "autoantibodies," in particular rheumatoid factor (RF) level. METHODS Three separate cohorts comprising a total of 972 patients with undifferentiated arthritis were studied for RA development (according to the 1987 American College of Rheumatology criteria) and arthritis persistence. The positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios (LRs) were compared between different levels of RF and the presence of anti-citrullinated protein antibody (ACPA). A similar comparison was made in 686 RA patients for the rate of joint destruction and achievement of sustained disease-modifying antirheumatic drug-free remission during 7 years of followup. The variation in RF levels obtained by different measurement methods in the same RF-positive sera was explored. RESULTS Compared to high RF levels, presence of ACPA had a better balance between positive LR and negative LR and between PPV and NPV for RA development. The additive value of ACPA assessment after testing for RF level was higher than vice versa. The association between high RF level and RA severity was not as strong as that between ACPA antibodies and RA severity. The RF level obtained by different methods in the same patients' sera varied considerably. CONCLUSION Our findings indicate that determination of RF level is subject to large variation; high RF level has limited additive prognostic value compared to ACPA positivity. Thus, omitting RF level and using RF presence, ACPA presence, and ACPA level may improve the 2010 criteria for RA. Show less
Objective. Recently, new classification criteria for rheumatoid arthritis (RA) have been devised by methodology that used first a quantitative approach (data from databases), then a qualitative... Show moreObjective. Recently, new classification criteria for rheumatoid arthritis (RA) have been devised by methodology that used first a quantitative approach (data from databases), then a qualitative approach (consensus; based on paper patients), and finally a common sense-based approach (evaluation of the former phases). Now the individual items that make up these criteria are being evaluated. This study was undertaken to analyze the item "autoantibodies," in particular rheumatoid factor (RF) level. Methods. Three separate cohorts comprising a total of 972 patients with undifferentiated arthritis were studied for RA development (according to the 1987 American College of Rheumatology criteria) and arthritis persistence. The positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios (LRs) were compared between different levels of RF and the presence of anti-citrullinated protein antibody (ACPA). A similar comparison was made in 686 RA patients for the rate of joint destruction and achievement of sustained disease-modifying antirheumatic drug-free remission during 7 years of followup. The variation in RF levels obtained by different measurement methods in the same RF-positive sera was explored. Results. Compared to high RF levels, presence of ACPA had a better balance between positive LR and negative LR and between PPV and NPV for RA development. The additive value of ACPA assessment after testing for RF level was higher than vice versa. The association between high RF level and RA severity was not as strong as that between ACPA antibodies and RA severity. The RF level obtained by different methods in the same patients' sera varied considerably. Conclusion. Our findings indicate that determination of RF level is subject to large variation; high RF level has limited additive prognostic value compared to ACPA positivity. Thus, omitting RF level and using RF presence, ACPA presence, and ACPA level may improve the 2010 criteria for RA. Show less
OBJECTIVE:: Recently new classification criteria for Rheumatoid Arthritis (RA) have been devised by methodology that used first a quantitative approach (data from databases), then a qualitative... Show moreOBJECTIVE:: Recently new classification criteria for Rheumatoid Arthritis (RA) have been devised by methodology that used first a quantitative approach (data from databases), then a qualitative approach (consensus-based on paper patients) and finally a common sense based approach (evaluation of the former phases). Now these criteria are being evaluated to assess characteristics of the individual items. This study analyzed characteristics of the item autoantibodies, in particular RF-level. METHODS:: Three separate cohorts with a total of 972 undifferentiated arthritis patients were studied for RA-development (according to the 1987 ACR criteria) and arthritis persistency. Positive and negative predictive values (PPV, NPV) and likelihood ratios (LR) were compared between different levels of RF and the presence of ACPA. A similar comparison was made in 686 RA-patients for the rate of joint destruction during 7 years of follow-up and achievement of sustained-DMARD-free-remission. The variation in RF-levels obtained by different measurement methods in the same RF-positive sera was explored. RESULTS:: Presence of ACPA had a better balance between LR+/LR- and PPV/NPV than high RF-levels for RA-development. The additive value of ACPA assessment after high level RF-testing was higher than vice versa. High level RF was less strongly associated with RA-severity than ACPA-antibodies. The RF-level obtained by different methods in the same patients' sera varied considerably. CONCLUSION:: Level determination of RF is subject to large variation; high level RF has limited additive prognostic value compared to ACPA-positivity. Thus, omitting RF level and using RF-presence, ACPA-presence and ACPA-level may improve the 2010 criteria for RA. Show less
Artac, H.; Reisli, I.; Kara, R.; Pico-Knijnenburg, I.; Adin-Cinar, S.; Pekcan, S.; ... ; Zelm, M.C. van 2010
Homozygous CD19 mutations lead to an antibody deficiency due to disruption of the CD19 complex and consequent impaired signaling by the B-cell antigen receptor. We studied the effects of... Show moreHomozygous CD19 mutations lead to an antibody deficiency due to disruption of the CD19 complex and consequent impaired signaling by the B-cell antigen receptor. We studied the effects of heterozygous CD19 mutations on peripheral B-cell development and antibody responses in a large family with multiple consanguineous marriages. Sequence analysis of 96 family members revealed 30 carriers of the CD19 mutation. Lymphocyte subset counts were not significantly different between carriers and noncarriers in three different age groups (0-10 years; 11-18 years; adults). B cells of carriers had reduced CD19 and CD21 median expression levels, and had reduced proportions of transitional (0-10 years) and CD5(+) B cells (adults). CD19 carriers did not show clinical signs of immunodeficiency; they were well capable to produce normal serum Ig levels and had normal responses to primary and booster vaccinations. The frequency of mutated V-kappa alleles was not affected. Heterozygous loss of CD19 causes some changes in the naive B-cell compartment, but overall in vivo B-cell maturation or humoral immunity is not affected. Many antibody deficiencies are not monogenetic, but likely caused by a combination of multiple genetic variations. Therefore, functional analyses of immune cell function should be carried out to show whether heterozygous mutations contribute to disease. Genes and Immunity (2010) 11, 523-530; doi:10.1038/gene.2010.22; published online 6 May 2010 Show less
