**4. Other autoantibodies**

especially in the context of SLE, Sjögren's syndrome, subacute cutaneous lupus and neonatal lupus congenital heart block [31, 32]. However, the presence of anti-Ro52 alone, without anti-Ro60, was reported in inflammatory myopathy and in systemic sclerosis. It was also observed, that anti-Ro52 antibodies are, to larger extent than anti-Ro60, associated with primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) with co-expression of anti SLA antibodies

Anti-SS-B/La antibodies are less common and usually coexist with anti-SS-A antibodies, and their presence in other systemic diseases, especially in SLE (25% of patients with TRU), is associated with skin lesions (erythema, alopecia), inflammation of the serous membranes, leukopenia, symptoms of dryness and they often coexist with the presence of anti-SS-A antibodies (secondary SS) [28]. Rao et al. have noted that anti-SSB antibodies are important for the SLE diagnosis. They are associated with cheek erythema, alopecia, serositis, secondary Sjögren's syndrome, and hematological changes such as leukocytopenia, thrombocytopenia, and immunoglobulins elevation. They are often accompanied by the presence of anti-/Ro or anti-SSA/Ro52 antibodies [34]. These autoantibodies may also be found before the SLE-

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

(soluble liver antibodies) [33].

124 Autoantibodies and Cytokines

*2.3.2. Anti-SS-B/La antibodies*

specific antibodies can be detected [35].

**3. Rheumatoid factor**

#### **4.1. Anti-centromere autoantibodies**

Anti-centromere antibodies (ACA) are directed to six antigens associated with centromere (composed of a complex of kinetochore proteins). Currently identified anti-centromere antibodies (CENP) have been assigned designations with letters from A to F. The most common are CENP-A, B and C. CENP-B is also the most frequently occurring anti-centromere antibody in patients with pSS. The incidence of ACA antibody described in the literature ranges from 3.7 to 4% [40, 41]. This antibody, with a mass of 80 kDa, is a DNA-binding protein involved in the heterochromatin folding. Anti-centromere antibodies (A, B, C) occur mainly in limited systemic sclerosis (LSSc) and are associated with the prevalence of telangiectasia, higher severity of Raynaud's symptom, lung involvement such as interstitial lung disease [ILD] and fibrosis [42]. Their relationship between the presence of ACA antibodies and the involvement of endocrine glands has been demonstrated; in the ACA+ group, anti-SS-A and anti-SS-B autoantibodies were less frequent [42].

The association of ACA antibodies with non-Hodgkin's lymphomas (CENP-F) including MALT lymphomas was also described [43], as well as the case reports of CENP-B presence in small-cell lung cancer [44].

Interestingly, it has also been demonstrated that the presence of anti-CENP-B antibodies is associated with prolonged survival in a breast cancer [45].
