**3. Rheumatoid factor**

Rheumatoid factor (RF) is an autoantibody directed against the CH2 and CH3 domains of an Fc region of a class G immunoglobulin (IgG). RF is produced by plasmatic cells (RF-PCs) that are formed from B cells activated both dependently and independently of T lymphocytes. Thus, RF producing B cells (RF-PC) become cells with ability of antigen presentation (APC) and of binding IgG. As this cascade of events constitutes a method of immune response against the infectious antigens, the RF production during infections protects the host organism. This phenomenon explains the occurrence of RF in the course of many viral (e.g., HCV, Herpes virus, and HIV), bacterial (e.g., subacute bacterial endocarditis, *Chlamydia pneumoniae*, *Klebsiella pneumoniae*, tuberculosis, and syphilis) and even parasitic (malaria, onchocerciasis, and toxoplasmosis) infections. In those autoimmune diseases, in which B-cell hyperactivity occurs, rheumatoid factors, particularly clinically relevant RF-IgM, also appears [36]. It should be remembered that RF appears in 4% of a healthy population and its incidence increases with age; after 75 years of life, RF can be observed even in 10–25% of individuals [37, 38]. The frequency (%) of RF in various CTD is presented in **Table 3**. The primary Sjögren's syndrome is one of the autoimmune diseases in which the majority of patients have a rheumatoid factor (some authors report up from 60 to 90% of patients)—specifically its most common IgM class isotype. The presence of RF IgM is associated with the occurrence of leukopenia, increased erythrocyte sedimentation rate (ESR), higher concentration of gamma globulins and lower C4 complement component concentration. Observations of a positive correlation of the rheumatoid factor with symptoms of dryness, hypergammaglobulinemia, presence of higher ANA antibody titers, presence of


**Table 3.** The frequency of RF in various connective tissue diseases [39].

anti-SS-A antibodies, anti-SS-B, increased ESR and leukopenia were presented in their work by Witte et al. [39]. The presence of RF in patients with pSS, as well as in other autoimmune diseases, and in acute infections, indicates the formation of a large number of other antibodies and the formation of antigen complexes with antibodies. The frequency of RF in various CTD was presented in **Table 3** [39].
