**2.3. Characteristics of ENA antibodies and their connection with primary Sjögren's syndrome**

From 1981, it is known [26] that SS-A/Ro antigens are associated with small cytoplasmic RNAs. In 1984 Ro60 kD protein was discovered and Ben-Chetrit et al. in 1988 demonstrated second part of SS-A/Ro complex—a 52 kD protein [25–27]. As we have recently learned, the SS-A/ Ro antigen consists of two different proteins Ro60 and Ro 52, with different gene localization: Ro60 is located on chromosome 19, while Ro-52 on chromosome 11. It was also revealed that these antigens, in physiological conditions, are found in different cell compartments. The detection of their presence determines different clinical implications. Presently, this problem needs still further investigation.

associated with the presence of antibodies against SS-A/Ro antigens, primarily Ro52KD and

**Figure 1.** Simplified algorithm of immunological diagnosis of rheumatic diseases [22–24]. ANA—antinuclear antibodies; DFS70—dense fine speckled pattern antibodies; ENAs—extractable nuclear antigens; dsDNA—anti-double stranded

Primary Sjögren's Syndrome and Autoantibodies http://dx.doi.org/10.5772/intechopen.75011 123

The formation of anti-SS-A is affected by the UV radiation, which increases the expression of antigens on the cell surface. Anti-SS-A/Ro antibodies are considered as a triggering factor for photosensitivity in SCLE and NLE, although patients with DLE, but without anti-Ro antibodies, present skin changes after sun/light exposition as well, probably due to other pathomechanism (the presence of autoantibodies/immunoglobulins between skin and the

Ro60 antigen attaches to uncoded RNA to form a complex (hY-RNA) that plays a role in inhibiting the immune response. Ro52 antigen is a phosphoprotein forming due to stimulation by

Autoantibody Ro60 has been associated with Sjögren's syndrome in particular but also occur in SLE (50%), and subacute cutaneous lupus (SCLE) (60%) and neonatal lupus (NLE) [31]. Anti-Ro antibodies in SLE and SCLE are associated with photosensivity and skin changes (SCLE, NLE). In SCLE, negative results for ANA screening or finding ANA in low titer do not exclude the presence of anti-SSA/Ro antibodies (antibody—negative SCLE). Anti-SS-A antibodies are also found in systemic sclerosis, RA and polymyositis, as well as dermatomyositis (PM/DM) and autoimmune hepatitis, with antibodies to the Ro52 antigen present more frequently. Anti-Ro52 antibodies frequently occur in association with anti-Ro60 antibodies,

is associated with a higher degree of inflammatory changes in the salivary glands.

viral infection, type I interferon pathway and through Toll-like receptors [28].

epidermis) [30].

DNA antibodies.

*2.3.1. Anti-SSA/Ro antibodies*

SS-A/Ro (60KD + 52KD) is a complex present on most cells, including platelets and red blood cells. It is considered that the anti-SS-A antibody plays a pathogenic role in pSS and its presence is associated with more severe symptoms, resulting from the involvement of endocrine glands, lymphadenopathy, larger salivary glandular infiltrates, characteristic vasculitis and longer duration of the disease [28, 29]. Also the occurrence of interstitial lung disease (ILD) is


RA—rheumatoid arthritis; pSS—primary Sjogren's syndrome; MCTD—mixed connective tissue disese; SLE—systemic lupus erythematosus; dSSc—disseminated systemic sclerosis, lSSc-localized systemic sclerosis; PM—polymyositis; DM—dermatomyosistis; GPA—granulomatosis with polyangiitis; MPA—microscopic polyangiitis.

**Table 2.** Autoimmune diseases and main autoantibodies [20–24].

**Figure 1.** Simplified algorithm of immunological diagnosis of rheumatic diseases [22–24]. ANA—antinuclear antibodies; DFS70—dense fine speckled pattern antibodies; ENAs—extractable nuclear antigens; dsDNA—anti-double stranded DNA antibodies.

associated with the presence of antibodies against SS-A/Ro antigens, primarily Ro52KD and is associated with a higher degree of inflammatory changes in the salivary glands.

The formation of anti-SS-A is affected by the UV radiation, which increases the expression of antigens on the cell surface. Anti-SS-A/Ro antibodies are considered as a triggering factor for photosensitivity in SCLE and NLE, although patients with DLE, but without anti-Ro antibodies, present skin changes after sun/light exposition as well, probably due to other pathomechanism (the presence of autoantibodies/immunoglobulins between skin and the epidermis) [30].

Ro60 antigen attaches to uncoded RNA to form a complex (hY-RNA) that plays a role in inhibiting the immune response. Ro52 antigen is a phosphoprotein forming due to stimulation by viral infection, type I interferon pathway and through Toll-like receptors [28].

#### *2.3.1. Anti-SSA/Ro antibodies*

SSB, SSC, Scl-70, PM-1, PM-Scl) [23]. The set of all ENA includes more than 100 soluble and cytoplasmic antigens. In clinical practice, until present day, only few of the them are finding use as a immunological hallmarks of certain autoimmune diseases or being used as immunological prognostic factors. Among them the most prominent are as follows: anti-RNP (antiribonucleoprotein anti-U(1)RNP), anti-Sm RNP, anti-SSA/Ro, anti-SSB/La, anti-Sm (Smith) antibody, anti-Scl-70 (anti-topoisomerase antibodies), anti-Jo-1 (anti-histidyl-transfer RNA synthase antibodies). The pattern of positive and negative results obtained with an ENA panel should be evaluated in conjunction with all clinical findings. Main autoantibodies and disease which they are typical to are presented in **Table 2**. Selected autoimmune diseases along with their predominant autoantibodies are presented in **Table 2**. **Figure 1** shows a

**2.3. Characteristics of ENA antibodies and their connection with primary Sjögren's** 

From 1981, it is known [26] that SS-A/Ro antigens are associated with small cytoplasmic RNAs. In 1984 Ro60 kD protein was discovered and Ben-Chetrit et al. in 1988 demonstrated second part of SS-A/Ro complex—a 52 kD protein [25–27]. As we have recently learned, the SS-A/ Ro antigen consists of two different proteins Ro60 and Ro 52, with different gene localization: Ro60 is located on chromosome 19, while Ro-52 on chromosome 11. It was also revealed that these antigens, in physiological conditions, are found in different cell compartments. The detection of their presence determines different clinical implications. Presently, this problem

SS-A/Ro (60KD + 52KD) is a complex present on most cells, including platelets and red blood cells. It is considered that the anti-SS-A antibody plays a pathogenic role in pSS and its presence is associated with more severe symptoms, resulting from the involvement of endocrine glands, lymphadenopathy, larger salivary glandular infiltrates, characteristic vasculitis and longer duration of the disease [28, 29]. Also the occurrence of interstitial lung disease (ILD) is

**Disease. RA pSS MCTD SLE dSSc lSSc PM DM GPA MPA**

RA—rheumatoid arthritis; pSS—primary Sjogren's syndrome; MCTD—mixed connective tissue disese; SLE—systemic lupus erythematosus; dSSc—disseminated systemic sclerosis, lSSc-localized systemic sclerosis; PM—polymyositis;

DM—dermatomyosistis; GPA—granulomatosis with polyangiitis; MPA—microscopic polyangiitis.

Anti-CENP-A,B,C

Anti-Jo-1 Ro-52 Other antisynthetase antibodies, Anti-Mi-2 Anti-SRP

Anti-Ro-52 Anti-Mi-2

cANCA pANCA

Anti-Scl-70

simplified diagnostic algorithm of immunological diagnosis.

**syndrome**

122 Autoantibodies and Cytokines

Antibodies ACPA

RF

Anti-SS-A/ Ro60 Anti-SS-A/ Ro52 Anti-SS-B/ LA RF

RNP RF

**Table 2.** Autoimmune diseases and main autoantibodies [20–24].

AntidsDNA Anti-Sm Anti-Ro60

needs still further investigation.

Autoantibody Ro60 has been associated with Sjögren's syndrome in particular but also occur in SLE (50%), and subacute cutaneous lupus (SCLE) (60%) and neonatal lupus (NLE) [31]. Anti-Ro antibodies in SLE and SCLE are associated with photosensivity and skin changes (SCLE, NLE). In SCLE, negative results for ANA screening or finding ANA in low titer do not exclude the presence of anti-SSA/Ro antibodies (antibody—negative SCLE). Anti-SS-A antibodies are also found in systemic sclerosis, RA and polymyositis, as well as dermatomyositis (PM/DM) and autoimmune hepatitis, with antibodies to the Ro52 antigen present more frequently. Anti-Ro52 antibodies frequently occur in association with anti-Ro60 antibodies, 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 (soluble liver antibodies) [33].
