The distinguishing of the IgG4-related disease (IgG4-RD) from among other rheumatic diseases has brought attention to the IgG4 subclass of immunoglobulins. It is the least numerous subclass among immunoglobulins G. In general, IgG4 is considered to be non-inflammatory and tolerance inducing, due to its unique structure. However, in IgG4-RD this antibody plays a pathogenic role in activation of the fibrinogenesis and of the inflammatory process; there are also suggestions that it may be a marker of an abnormal inflammatory response. The importance of IgG4 for the pathogenesis of allergic diseases, with a vital role of its ratio to immunoglobulin E (IgE/IgG4 ratio), has been known for years. The role of IgG4 in the course and pathogenesis of rheumatic diseases is still being researched and is not yet fully understood. Increased IgG4 levels have been revealed in rheumatoid arthritis, although no clear link between this phenomenon and disease activity has been demonstrated. There are articles on the potential importance of IgG4 concentration (of both elevated and decreased serum levels) in Sjogren’s syndrome. Additionally, anti-nuclear IgG4 antibody significant titers have been detected in SLE patients, and it has been suggested that the effect of these antibodies on complement consumption and the production of proinflammatory cytokines may play a role in inhibiting the progression of SLE. IgG4 plays a role in autoimmune diseases other than rheumatic diseases, such as pemphigus, bullous pemphigoid, idiopathic membranous glomerulonephritis, or myasthenia gravis, but also in helmints infections. Research shows the importance of IgG4 in malignancy of neoplasms. Melanoma cells are known to stimulate IgG4 production through a modified Th2-based inflammatory response. The role of this immunoglobulin in cholangiocarcinoma is also considered as possible. The aim of this review article is to discuss the current knowledge of IgG4 not only from the perspective of the IgG4-RD but also from a point of view of other autoimmune diseases with particular emphasis on rheumatic diseases.

Since the discovery of penicillin by Fleming in 1928, the knowledge of the antibiotics’ spectrum and mechanism of action has been steadily increasing. Antibiotics became an effective tool in the fight against many pathogens, changing the prognosis of outcome for many serious diseases. It is already known that antibiotics not only have the antibacterial activity, but many of them—e.g. macrolides, sulphonamides and tetracyclines—have immunomodulating effect, affecting functions of lymphocytes, macrophages and costimulatory molecules, macrophage migration and phagocytosis, as well as proinflammatory cytokine secretion. The expanding knowledge of the effects of antibiotics on the immune system has brought with it new applications of antibiotics in organ transplantation, invasive cardiology and treatment of autoimmune diseases such as rheumatoid arthritis or asthma.

ObjectivesIn inflammatory bowel disease (IBD), characterized by chronic mucosal inflammation, rheumatic abnormalities ranging from arthralgia to spondyloarthritis (SpA) are the most common extraintestinal manifestations. The pathogenesis of IBD-related arthritis is unclear. In this study, we search for clinical and immunological differences between patients with IBD-associated spondyloarthritis and IBD patients without SpA symptoms.Material and methodsPatients with an established diagnosis of IBD, suffering from Leśniowski-Crohn disease (L-CD, n = 24) or ulcerative colitis (UC, n = 27), were enrolled in the study. Clinical evaluation of patients, based on medical history, blood tests, physical and radiological examinations, allowed two subgroups of patients to be established. One subgroup comprised patients fulfilling criteria for both IBD and SpA (IBD + SpA, n = 29), while the other included IBD patients with arthralgia only (IBD, n = 22). Serum concentrations of interleukins (IL-6, IL-10, IL-21, IL-22, IL-23) and interferon γ (IFN-γ) were measured by specific enzyme-linked immunosorbent assays (ELISA).ResultsPatients with IBD + SpA were characterized by shorter disease duration (3 vs. 9 years), higher frequency of HLA-B27 positivity (60.7% vs. 4.5%) and uveitis (20.7% vs. 0%), compared with the IBD subgroup. The serum concentrations of C-reactive protein (CRP) and tested cytokines did not differ between IBD + SpA and IBD patients, or between L-CD and UC groups. However, in the IBD + SpA subgroup there was weak to moderate positive correlation between serum concentrations of CRP and several cytokines (IL-6, IL-21, IFN-γ), and additional moderate positive correlation between serum concentrations of IL-23 and clinical activity of SpA. By contrast, in IBD subgroup a strong inverse correlation between serum concentrations of Interleukin 23 and CRP was found.ConclusionsIBD-related spondyloarthritis occurs relatively early, affects mostly HLA-B27(+) individuals, and is often accompanied by ocular involvement. In these patients several circulating cytokines are associated with systemic inflammation. IL-23 seems to be protective in IBD while detrimental in IBD-related spondyloarthritis.

ObjectivesInflammatory bowel disease (IBD) and spondyloarthritis (SpA) have some overlapping clinical features, i.e. gut and joint inflammation. Cytokines of interleukin 17(IL-17)/IL-23 axis play a pathogenic role in both diseases. Integrins (ITGs) regulate migration of immune cells to inflamed tissues (ITGβ7 into gut, ITGβ2 into gut and also to other tissues). In this study, we search for differences in the serum concentrations of these cytokines and integrins between patients suffering from SpA or IBD with and without overlapping symptoms.Material and methodsPatients with SpA (n = 30), IBD (n = 68), and healthy volunteers (n = 28) were included in the study. Fourteen SpA patients reported symptoms characteristic for IBD. Spondyloarthritis symptoms were diagnosed in 50% of IBD patients, while other patients of this group reported arthralgia only. Serum concentrations of IL-17, IL-22, IL-23, ITGβ2, and ITGβ7 were measured by specific enzyme-linked immunosorbent assay using commercially available sets. The Mann-Whitney and Spearman’s rank tests were used for intergroup comparison and correlation assessment, respectively.ResultsComparison of patient groups showed significantly higher serum concentrations of IL-17, IL-22, and ITGβ7 in SpA, and up-regulated levels of IL-23 in IBD patients. Similar differences were observed between patient subgroups, both with and without overlapping symptoms. In SpA but not in IBD patients, serum concentrations of ITGβ7 inversely correlated (r = –0.552) with C-reactive protein.ConclusionsPatients with SpA and IBD differ in the circulating concentrations of IL-17/IL-23 axis cytokines and ITGβ7, irrespectively of the presence or absence of overlapping symptoms. Therefore, we conclude that observed differences are attributed rather to underlying than concurrent disease.

BackgroundThe useful tool to assessing disease activity in primary Sjögren’s syndrome(pSS) is an EULAR Sjögren’s syndrome disease activity index (ESSDAI)[.1,2 ObjectivesThe aim of this study was indication of laboratory and clinical factors affecting the ESSDAI in pSS patients.Methods75 pSS patients were included; 65 (87%) female, 10 (13%)men; mean age 50 years SD ±15. The tests included:basic laboratory tests, rheumatoid factor (RF), erythrocyte sedimentation rate, CRP, gammaglobulins serum concentration, C4 and C3 component of complement, antinuclear antibodies (ANA) - IF test HEp-2000, anti-SS-A and anti-SS-B antibodies evaluation with semi-quantitative immunoblotting, standard ELISA assays for serum cytokines levels (BAFF, APRIL, FLT-3L, TNF-β, IL-21) and β2-microglobulin. Biopsy of minor salivary gland with the histopathological evaluation (focus score-FS) and the immunochemistry was also performed with the CD3+, CD4 +, CD19 +, CD21 +, CD35 +cells presence assessment. The Schirmer’s test and ocular staining score (OSS) were performed. The Bioethics Committee aproval was obtained. Statistics: U Mann-Whitney (continuous variables) tests, Spearman correlation coefficient (correlations between quantative variables) with statistical significance set at p<0.05.ResultsESSDAI depends on FS, the presence of CD4 +, CD3 +cells in the minor salivary glands infiltrates, RF and cryoglobulins (p<0.05). The division of pSS subjects into two subgroups (ESSDAI >5;<5) revealed, that the autoantibodies as anti-SS-A and anti-SS-B, influence the severity of the disease (p=0,046; p=0015 respectively). ESSDAI positively correlated with OSS, but not with the Schirmer’s test, other tested cytokines, ESR, CRP and gammaglobulins concentration - yet interestingly ESSDAI correlates negatively with IgG4 (rho=-0,435).ConclusionsThe results confirm, that organ-related complications are influenced by inflammatory activity. This activity is expressed by mononuclear cell infiltrates (FS), which consist primarily of T-lymphocytes (indicators of active and early stage inflammation). However, contrary to other observations,3 no correlation between ESSDAI and cytokines or β2- microglobulin was found. The correlation of ESSDAI with the presence of pSS marker autoantibodies (anti-SS-A, anti SS-B antibodies), as well as with non-specific ones (RF or cryoglobulins), indicates the immunological disease activity and overactivity of B lymphocytes as suspected. The reduction of IgG4 concentration in pSS patients correlating with higher ESSDAI can be associated with breaking the autotolerance and lack of stimulation of IgG4 production. But the role and importance of IgG4 in immunological processes both as an activator of dependent autoimmune diseases and, on the other hand, the marker of induction of immune tolerance requires further research.References[1] Seror R, Bowman SJ, Brito-Zeron P, et al. EULAR Sjögren’s syndrome disease activity index (ESSDAI): a user guide. RMD Open2015;1: e000022.[2] Risselada AP, Kruize AA, Bijlsma JW. Clinical applicability of...