WHAT IS RHEUMATOID ARTHRITIS (RA)?
Rheumatoid arthritis is a chronic systemic auto-immune disorder predominantly affecting synovial joints.
Not too frequently but directly or indirectly It also affects tissues other than those in joint; like blood, skin, pleura, lungs, kidney nerves, heart, pericardium, blood vessels, eyes, liver etc.
CAUSES OF RHEUMATOID ARTHRITIS (RA)
Its still unclear how its caused but its believed to be combination of
HLA-DR4 is storngly associated with Rheumatoid Arthritis but not in all ethnicity it shows the same significance
MHC class II related allotypes and T-cell Associated Protein PTPN22 are also found to be associated with RA
2) Environmental and Lifestyle Factors
Environmental factors like pollution ; lifestyle like addiction to cigarette smoking mental and physical stress and digestive disturbances are also doubted (though unconfirmed) ; hormonal fluctuations like during pregnancy/ menopause / hormonal medications are also believed to be strong contributing factors . still we are not able to link any infectious agent or vector associated to RA
PATHOGENESIS AND PATHOPHYSIOLOGY OF RHEUMATOID ARTHRITIS (RA)
Its been observed that there is abnormal immune response where there is a state of persistent cellular activation; due to constant positive feedback which may be due to inhibition of negative feedback pathway or exaggerated positive feedback due to certain factors; causing formation of immune complexes and autoimmunity which most of the times initially shows up in synovial joint and less frequently or later in other organs and tissues as well
Rheumatoid Arthritis manifests in following phases :-
Initial phase shows non specific inflamation
Amplification phase , caused by T-cell Activation
Chronic inflamatory Phase, where Cytokines like Interlukine-1 Interlukine-6 Tumour Necrosis Factor-alpha comes in picture causing chronic inflamation and tissue injury
Antibodies to IgGFc are called Rheumatoid Factor (RF/ RA factor) and Antibodies to Citrulinated Peptides (ACPA) are major factors specific in pathology of Rheumatoid Arthritis
Other nonspecific factors are abnormally Glycosylated Antibodies which are believed to be the contributing factors in arthritis though they are not specific to Rheumatoid Arthritis and are also present in many other Autoimmune conditions
B lymphocytes → Plasma cells → RA factor and ACPA(of IGg And Igm Classes) + Fc receptors & compliment (binding due to antibody’s altered N glycans) (simultaneously; doubted TNF activation at this Stage) → macrophage activation → synovial macrophage & dendritic cells further expresses MHC class II molecules → synovial oedmatous inflamation with T cell activation(also doubted TNF activation through T cell product IL17) and infiltration(mainly CD4 and CD8)→ intense inflamation -granulation tissue formation -angiogenesis-inflamatory products damaging tissues- thickening of synovium- cartilage disintegration -bone disintegration-joint degeneration.
Its observed that presence of B cell and T cell at site is not necessary for the pathogenesis; so their exact role is doubted also TNF a major foctor responsible for progress of Rheumatoid Arthritis is doubted that wether its predominantly derived through B cell or T cell channel or both as presented in above flow chart.
Other factors like IL1 ,IL6, IL15, IL17 are also believed to be important in pathogenesis of Rheumatoid Arthritis
DIAGNOSIS OF RHEUMATOID ARTHRITIS (RA)
may not show any changes in early stages though sometimes mild soft tissue swelling might be visible in later stages along with soft tissue swelling it may show juxta-articular osteopenia and loss off joint space in advanced stage it may also show nodes bony erosion subluxation of affected joints
Test for RA factor -non specific test; as its also seen in conditions like SLE,Sjogren’s syndrome,hepatitis C, other chronic infections, and also in 10% healthy individuals
Test for ACPA (measured as Anti-CCP antibodies) -specific test
Though negative RA factor or negative anti-CCP test doesnt rule out RA
Patients with clinical features and all other investigations pointing towards Rheumatoid Arthritis but RA Factor and Anti-CCP tests are called seronegative Rheumatoid Arthritis cases almost 25% cases falls in this category.
a new Serological test has been introduced called POCT point of care test where in; RF and anti-MCV are detected which has sensitivity of 72% and specificity of 99.7%
other non specific or/and indirect tests are
ESR; CRP; CBC;RFT;LFT;ANA;Ferritin levels;
incomplete article ; still under construction