Index. Note: Page numbers of article titles are in boldface type.

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1 Index Note: Page numbers of article titles are in boldface type. A AB1010 kinase inhibitor, 369 Abatacept, 264, 395 Activation-induced cytidine deaminase, Activity, disease. See Disease activity measurement. Adalimumab, 393 Aging, immune. See Immune aging. AIN457 (anti-interleukin-17 antibody), 356, 394 AMBITION study, of tocilizumab, American College of Rheumatology, RA criteria of, , Amyloid A, 278 Anakinra, 394, 413 Angiogenesis, , 411 Antibodies to citrullinated protein antigens (ACPAs), 214, 216, , Antigen-presenting cells fibroblast-like synoviocytes as, 314 T-cell interactions with, Antikeratin antibodies, 214, 216 Antiperinuclear factor antibodies, 214 Antithymocyte globulin, 336 APERA (standard protocol to evaluate rheumatoid arthritis), 250 Apoptosis-associated speck-like protein, 280 APRIL (a proliferation-inducing ligand), APT070 complement derivative, 283 ARRY-162 kinase inhibitor, 369, Arthritis, undifferentiated, evolution of, AS kinase inhibitor, Atacicept, Atherosclerosis. See Cardiovascular disease. Auranofin, 278 Autoantibodies. See also specific autoantibodies. in diabetes mellitus, in preclinical RA, , 226 in systemic lupus erythematosus, B B cell(s) regulatory, 317, 328 T-cell interactions with, Rheum Dis Clin N Am 36 (2010) doi: /s x(10) rheumatic.theclinics.com X/10/$ see front matter ª 2010 Elsevier Inc. All rights reserved.

2 428 Index B cell therapies, chemokine inhibition, 330, cytokine blockade, 330, history of, limitations of, rationale for, targets for activation and costimulation, , plasma cells, 331, survival and differentiation, 330, universal depletion, , 330, 395 BAFF protein (B lymphocyte activation factor), 318, Baminercept, 334 Behandelstrategieën voor Reumatoide Artiritis (BeSt) study, of activity measurement, 244 Belimumab, 333 B7-H3, of fibroblast-like synoviocytes, 314 Bim protein, 272 Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS), Blood vessels, growth of, in synovium, BMS-066 kinase inhibitor, 377 Body weight, cardiovascular disease and, Bone loss, as therapeutic target, B cell depletion for, 395 cytokines in, , osteoblasts in, 387, 389 osteoclasts in, , 389 Wnt proteins in, Bortezomib, 336 BRAGGSS (Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate), Bruton s tyrosine kinase, as therapeutic target, 376 C C5 gene, mutations of, Cadherin-11, CAMERA trial, of activity measurement, 244 Cardiovascular disease immune aging and, 306 in RA, pathogenesis of, prevention of, prognosis and, risk assessment in, treatment effects on, Caspases, b-catenin, in bone loss, 388 CCL20, CD28, in aging,

3 Index 429 CD134 (OX40), 315 CD275 (inducible costimulator) and ligand, 317 CD278 (inducible costimulator) and ligand, 317 Certolizumab, 393 Cgi1746 kinase inhibitor, 376 Chaperonin 10, CHARISMA trial, of tocilizumab, Chemokines in preclinical RA, 215 inhibition of, pathologic effects of, , Cholesterol levels, 408 CIMESTRA (Cyclosporine, Methotrexate, Steroid in RA) trial, 244 Citrullinated peptide antibodies, antibodies to, , , Clinical disease activity index (CDAI), 249 Clodronate, Complement pathways, Composite genetic risk score, 265 Compound 4 kinase inhibitor, 376 Congestive heart failure, Coronary artery disease. See Cardiovascular disease. Corticosteroids, 412 CP kinase inhibitor, 369, C-reactive protein in cardiovascular disease, 410 in disease activity, in preclinical RA, 215, 217, 232 CTLA-4 protein defects of, in antigen-presenting cells, 315 Cultural differences, in health questionnaires, 248 Cyanopyrrole 8, 375 Cyclosporine, Methotrexate, Steroid in RA (CIMESTRA) trial, 244 Cytidine deaminase, activation-induced, in synovium, Cytokines, 274 for B cell blockade, in bone loss, , in preclinical RA, 215, 217 of Th17 cells, D Danger-associated molecular patterns, 276, 278 Dendritic cells, Denosumab, 392 Diabetes mellitus, preclinical, Dickkopf proteins, in bone loss, 388 Disease activity measurement, challenges of clinical measures, 244 laboratory tests,

4 430 Index Disease (continued) patient self-reports, physician measures, disconnect with outcome, 249 history of, indices for, standard protocol for, value of, 244 Disease activity score (DAS/DAS28), Disease-modifying antirheumatic drugs cardiovascular disease and, 412 osteoblast function and, 387 tocilizumab with, 394 E Eculizumab, Endothelial cells, leukocyte interactions with, Endothelial progenitor cells, 411 Environmental factors, in preclinical RA, , 225 Eritoran, 278 Erythrocyte sedimentation rate, for disease activity, Etanercept, 318, 351, Extracellular signal-regulated kinases (ERKs), as therapeutic targets, F Fc receptors, 286 Fibroblast-like synoviocytes antigen-presenting action of, 314 autocrine interactions of, B-cell interactions with, 318 homotypic interactions of, T-cell interactions with, Fillagrin, antibodies to, 214, 216 Finnish Combination Treatment Trial, 244, 249 Folate antagonists, 274 FR kinase inhibitor, 371 Fractaline and receptor, 313 FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months) study, G Gender differences, in health questionnaires, 248 Genetic factors, in RA, cardiovascular disease and, 409 drug specificity and, functional studies of, genotype-phenotype studies, overview of,

5 Index 431 preclinical, , 225 risk alleles, , treatment failure and, 265 Genome-wide association studies, Genotype-phenotype studies, Germinal centers, in synovium, Golimumab, 393 gp96 glycoprotein, 278 GW2580 kinase inhibitor, 375 H Health Assessment Questionnaire and modifications, Heart failure, congestive, Heat shock proteins, 278 High-mobility group box chromosomal protein 1, 278 Homocysteine levels, Human leukocyte antigens in immune aging, 301 in RA cardiovascular disease and, 409 drug efficacy and, preclinical, Hyaluronic acid, 278 Hydroxychloroquine, 278, Hypertension, control of, 414 I Imatinib, 369, Immune aging, accelerated, autoimmunity and, evidence for, in RA, pathogenic effects of, Immunity, innate. See Innate immunity. INCB kinase inhibitor, 369 INCB18424 kinase inhibitor, Indolamine dioxygenase, 315 Inducible costimulator and ligand, 317, 329, 332 Infections, innate immunity to, Inflammasomes, Inflammation cardiovascular disease and, in preclinical RA, , 226 Toll-like receptors in, Infliximab, 393 cardiovascular disease risk of, 413 mechanism of action of, 275, 318

6 432 Index Innate immunity, See also specific components. complement pathways in, dendritic cells in, Fc receptors in, monocytes and macrophages in, pattern-recognition receptors in, Insulin resistance, Interleukin(s), 334 Interleukin-1 in bone loss, inhibitors of, 394 Interleukin-1b converting enzyme, 280 Interleukin-6 receptor, inhibitors of, , 394 Interleukin-6, in bone loss, Interleukin-7, 316 Interleukin-12, inhibitors of, Interleukin-15, Interleukin-17 and Th17 cells, cytokines expressed by, differentiation of, in bone loss, 391 in RA animal models of, 348 cardiovascular disease and, 410 inhibition of, neutralization of, role of, inhibitors of, trafficking of, 347 Interleukin-21, 349 Interleukin-22 and receptor, 349 Interleukin-23, 349 inhibitors of, J Janus kinases, as therapeutic targets, Joint counts, , c-jun N-terminal kinases (JNKs), inhibitors of, K Keratin, antibodies to, 214, 216 Ki20027 kinase inhibitor, 375 Kinases, as therapeutic targets, mitogen-activated protein kinases, receptor activator of nuclear factor-kb kinase, tyrosine kinases, c-kit inhibitors,

7 Index 433 L Leflunomide cardiovascular disease and, 412 mechanism of action of, 273 Leiden criteria, for RA, 225 Leukocytes, endothelial cell interactions with, LFM-A13 kinase inhibitor, 376 Linkage disequilibrium, Lipoprotein profile, 408 Low-density lipoprotein receptor-related protein, in bone loss, 388 LUNDEX disease activity measure, 249 LY (anti-interleukin-17 antibody), , Lymphocytes, endothelial cell interactions with, 320 Lymphotoxin blockade, 334 M Macrophage(s), Macrophage colony-stimulating factor, 375, 386 Magnetic resonance imaging, for disease activity, 248 Masitinib, 376 Mean overall index for rheumatoid arthritis (MOI-RA), 249 Metabolic syndrome, Methotrexate abatacept with, 395 cardiovascular disease and, 412 for B cell depletion, mechanism of action of, 273, 275 pharmacogenetics of, 265 tocilizumab with, Mitogen-activated protein kinase-extracellular signal-regulated kinases (MAPK-ERKs), as therapeutic targets, Mitogen-activated protein kinases, as therapeutic targets, Monocyte(s), Monocyte chemoattractant protein-1, 215, 217 N NALP proteins, Natural killer cells, 317 Neovascularization, 411 Neutropenia, due to tocilizumab, 355 Neutrophils, endothelial cell interactions with, 319 NOD proteins, 279 Nonsteroidal antiinflammatory drugs, Norfolk criteria, for RA, 225 Nuclear factor-kb kinase inhibitors, 318, Nucleotide-binding oligomerization domain-like receptors, 279

8 434 Index O OPTION trial, of tocilizumab, 353 Oral contraceptives, RA risk and, Osteoblasts, in bone loss, 387, 389 Osteoclasts, in bone loss, , 389 Osteopontin, 318 Osteoprotegerin, , OX40/OX40L, 315 P p38 inhibitors, Pamapimod, 369 Pathogen-associated molecular patterns, 276 Pattern-recognition receptors, PD kinase inhibitor, Perinuclear factor, antibodies to, 214 Pharmacogenetics, 265 PHOENIX trials, of ustekinumab, Plasma cells, depletion of, 331, Platelet derived growth factor receptor inhibitors, Preclinical rheumatoid arthritis, animal models of, autoantibodies in, , 226 clinically apparent disease development from, definition of, environmental factors in, , 225 evaluation of, 228, future research in, 229, genetic factors in, , 225 inflammation in, , 226 predictive models and, studies of, versus other autoimmune diseases, Proliferation-inducing ligand (APRIL), Protein phosphatase 22, 217, Q Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) data base, 249 Questionnaires, for disease activity, R R788 Sky inhibitor, 286, 369, 374 R406 spleen tyrosine kinase inhibitor, , 374 RA. See Rheumatoid arthritis. RADIATE trial, of tocilizumab, 353 RANK-L. See Receptor activator of nuclear factor-kb and ligand.

9 Index 435 Receptor activator of nuclear factor-kb and ligand, 318 blockade of, in bone loss, on B cells, 318 Receptor activator of nuclear factor-kb kinase, Retinoic acid-inducible gene I-like receptors, 280 Rheumatoid arthritis autoantibodies in. See Autoantibodies; specific autoantibodies. bone damage in, cardiovascular complications of, 306, comorbidities of, development of, disease activity measurement in, environmental factors in, , 225 evaluation of, 228, genetic factors in. See Genetic factors. immune aging in, inflammation in. See Inflammation. innate immunity and, phases of, preclinical, predictive models and, synovial cell-cell interactions, Rheumatoid arthritis treatment cardiovascular disease risk in, genetic factors in, preclinical, 228 targets for B cells, bone damage mechanisms, chemokine inhibition, 330, complement, Fc receptors, 286 interleukin-17, kinases, macrophages, plasma cells, 331, Rh cells, tryptophan degradation, 315 Rheumatoid factor, in preclinical RA, , RIG-1 protein, 280 Rituximab, 395 cardiovascular disease risk of, 413 for B cell depletion, RORC protein, in Th17 regulation, 346 ROR g t protein, in Th17 regulation, 346 S SAMURAI trial, of tocilizumab, 354 SATORI trial, of tocilizumab, 354 Secreted frizzled-related proteins, in bone loss, 388

10 436 Index Secretory phospholipase A2, 217 Simplified disease activity index (SDAI), Single nucleotide polymorphisms, in RA, Smoking cardiovascular disease risk of, 414 RA risk and, , 225 SP kinase inhibitor, Spleen tyrosine kinase (Syk) inhibitor, , 374 Standard protocol to evaluate rheumatoid arthritis (SPERA), 250 Statins cardiovascular effects of, 415 mechanism of action of, 264 preclinical, 228 Sulfasalazine cardiovascular disease and, 412 mechanism of action of, 273 Syk (spleen tyrosine kinase) inhibitor, , 374 Synoviocytes, fibroblast-like, cell-cell interactions of, Synovium, cell-cell interactions in, B cells, fibroblast-like synoviocytes, leukocytes, T cells, Systemic lupus erythematosus, preclinical, T T cells B-cell interaction with, costimulation of, inhibitors of, 395 fibroblast-like synoviocyte interactions with, interleukin-17, subsets of, in cardiovascular disease, 410 T-cell receptor excision circles, 300, 302 Telomeric erosion, Tenascin-C, 278 Thiazolidinediones, Thymus, aging of, 297 Thyroid dysfunction, cardiovascular disease in, TICORA (Tight Control of RA) study, 244 Tocilizumab, 318, , 394 Toll-like receptors, , 333 TOWARD trial, of tocilizumab, 353 TRAF1 gene, mutations of, Tryptophan degradation, 315 Tumor necrosis factor-a in bone loss, 389 inhibitors of, 334, 349 cardiovascular disease risk of, for bone loss, 393 mechanism of action of, 273

11 Index 437 Tumor progression locus inhibitors, Tyrosine kinases, as therapeutic targets, U Ultrasonography, for disease activity, 248 Undifferentiated arthritis, evolution of, Ustekinumab, V Vascular endothelial growth factor, 354, 376 Vasculogenesis, , 411 VX-702 kinase inhibitor, 369 W Wnt proteins, in bone loss, Women s Health Study, 215