To address the selective and persistent problem associated with RA therapy, using the universal anti-fluorescein isothiocyanate (FITC) chimeric antigen receptor T cells (CAR-T cells) coupled with FITC-labeled antigenic peptide epitopes, scholars developed a tailored therapeutic strategy that eliminates recognizing B cell subsets. associated with progressive disability, systemic complications, and early N-ε-propargyloxycarbonyl-L-lysine hydrochloride death [1,2]. RA is characterized by synovial inflammation and hyperplasia, production of autoantibodies including rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA), cartilage and bone deformities, and systemic features including cardiovascular, pulmonary, psychological, skin, and skeletal disorders [2]. In recent decades, we have obtained new genetic and pathogenetic insights along with new developments in RA disease assessment and therapeutic strategies, which have led to the approval of a variety of novel therapies [3]. In this review, we focus on the roles of diverse immune cells along with the wide spectrum of molecular mechanisms involved in the pathogenesis and clinical expression of RA, as well as their possible contribution to treatment response and precision medicine. 2. Epidemiology Most epidemiological studies in RA have been conducted in Western countries, showing an RA prevalence in the range of 0.5C1.0% in the US [4]. In general, women are 2C3 times more likely to develop RA than men. Indeed, the cumulative lifetime risk of developing adult-onset RA has been roughly estimated at 3.6% for women and 1.7% for men [5,6]. RA has a strong genetic component. Twin studies have estimated the heritability of RA to be approximately 60% [7]. This number is observed in ACPA-positive patients, while estimates of seronegative diseases are lower. However, the disease concordance of identical twins is only 12C15%, indicating that environmental factors also play an important role in susceptibility. About 100 loci have been identified across genomes harboring RA susceptibility variants by genome-wide association studies [8,9,10], with fine mapping [11], candidate gene approaches [12,13], and a meta-analysis of genome-wide association studies involving 100,000 individuals [14]. In particular, specific class II human leukocyte antigen (HLA; also known as major histocompatibility complex (MHC)) loci, which encode MHC molecules that may contain a shared epitope, show a very strong susceptibility to RA, consistent with classical findings [15]. Smoking, silica exposure, and periodontal disease are environmental risk factors for developing RA [16,17,18]. Both genetic and environmental risk factors contribute to RA, and multiple risk factors may be required before the threshold at which RA is triggered. Disease progression includes asymptomatic synovitis and the initiation and dissemination of autoimmunity against altered auto-proteins that can occur years before clinical symptoms begin [3]. N-ε-propargyloxycarbonyl-L-lysine hydrochloride 3. Diagnosis The diagnosis of RA is based on the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria (Table 1) [19]. Application of these criteria provides a score of 0C10, with a score of 6 being satisfactory for the diagnosis of definite RA. The 2010 ACR/EULAR criteria included serologic testing (RF or ACPA). The diagnostic criteria for ACPA are presentation of an Rabbit Polyclonal to RPL12 early disease course and prediction of an aggressive disease course [20]. Table 1 The 2010 ACR/EULAR classification criteria for RA. thead th colspan=”2″ align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ Classification Criteria for RA (Total Score 6 is Considered Satisfactory for the Diagnosis of RA) /th th align=”center” valign=”middle” style=”border-top:solid thin;border-bottom:solid thin” rowspan=”1″ colspan=”1″ Score /th /thead joint involvement br / (swollen or tender joint)1 large joint (shoulders, elbows, hips, knees, and ankles)02C10 large joints11C3 small joints (with or without involvement of large joints) *24C10 N-ε-propargyloxycarbonyl-L-lysine hydrochloride small joints (with or without involvement of large joints)3 10 joints (at least 1 small joint) **5serologyNegative RF and negative ACPA (upper limit of normal (ULN))0Low-positive RF or low-positive ACPA (ULN and 3 times)2High-positive RF or high-positive ACPA (3 times)3acute-phase reactantsNormal CRP and normal ESR0Abnormal CRP or abnormal ESR1duration of symptoms 6 weeks06 weeks1 Open in a separate window CRP = C-reactive protein; ESR = erythrocyte sedimentation rate. * Small joints refers to the metacarpophalangeal joints, proximal interphalangeal joints, second through fifth metatarsophalangeal joints, thumb interphalangeal joints, and wrists. **.