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Einleitung: Primäre Immundefekte, wie Antikörpermangel-Syndrome, gehen oft mit einer verminderten Lebensqualität einher, da die Erkrankung als Belastung erlebt wird. Im Sinne einer aktiven Krankheitsbewältigung kommt neben der konventionellen Therapie auch Komplementär- und [zum vollständigen Text gelangen Sie über die oben angegebene URL], Deutscher Rheumatologiekongress 2020, 48. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 34. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh)

Hypophosphatasia (HP) is a rare inborn error of bone and mineral metabolism transmitted as an autosomal- recessive trait. It is characterized by a reduced activity of the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSAP) and elevated concentrations of its substrates including pyrophosphates. Clinical symptoms include defective bone mineralisation with bone deformities, fractures and recently defined chronic non-bacterial osteomyelitis. Renal damage due to calcification, dental abnormalities with premature loss of dentition and craniosynostosis are further symptoms. Knowledge on the mechanisms underlying cell activation leading to inflammation and tissue destruction is still limited in HP. Recent investigations have provided evidence that calcium pyrophosphate crystals are essentially involved in activating inflammatory signal transduction pathways via different receptors of the innate immune system. Further studies are needed to improve our understanding of the pathophysiological mechanisms leading to inflammation and tissue destruction associated with deposition of microcrystals. They might support the development of new therapeutic strategies for crystal-induced inflammation. Laboratory assays, genetic analysis and radiographic imaging can confirm the diagnosis. Since clinical symptoms are highly variable patients should be followed by a HP-experienced multidisciplinary team (paediatrician, radiologist, orthopedic surgeon, neurosurgeon, dentist, nutritional specialist). At the moment symptomatic treatment is most important because curative or causative therapies, like gene transfer or enzyme replacement therapy, are not yet available.

Objective: Myasthenia gravis (MG) is an autoimmune condition in which neurotransmission is impaired by binding of autoantibodies to acetylcholine receptors (AChR) or, in a minority of patients, to muscle specific kinase (MuSK). There are differences in the dominant IgG subclass, pathogenic mechanisms, and treatment responses between the two MG subtypes (AChR or MuSK). The antibodies are thought to be T-cell dependent, but the mechanisms underlying their production are not well understood. One aspect not previously described is whether defects in central and peripheral tolerance checkpoints, which allow autoreactive B cells to accumulate in the naive repertoire, are found in both or either form of MG. Methods: An established set of assays that measure the frequency of both polyreactive and autoreactive B cell receptors (BCR) in naive populations was applied to specimens collected from patients with either AChR or MuSK MG and healthy controls. Radioimmuno-and cell-based assays were used to measure BCR binding to AChR and MuSK. Results: The frequency of polyreactive and autoreactive BCRs (n = 262) was higher in both AChR and MuSK MG patients than in healthy controls. None of the MG-derived BCRs bound AChR or MuSK. Interpretation: The results indicate that both these MG subtypes harbor defects in central and peripheral B cell tolerance checkpoints. Defective B cell tolerance may represent a fundamental contributor to autoimmunity in MG and is of particular importance when considering the durability of myasthenia gravis treatment strategies, particularly biologics that eliminate B cells.

Ein bislang gesunder neun Monate alter Säugling präsentierte sich mit fulminantem Verlauf einer Pneumokokkenmeningitis mit Sepsis und disseminierter intravasaler Gerinnung. Trotz umgehender Einleitung intensivmedizinscher Maßnahmen und einer wirksamen Antibiotikatherapie verstarb der [for full text, please go to the a.m. URL], 21. Jahrestagung der Deutschen Gesellschaft für Pädiatrische Infektiologie (DGPI)

Objective Chronic non-bacterial osteomyelitis CNO is an inflammatory disorder of the musculoskeletal system with unknown etiology. In addition to bone inflammation, patients may present with inflammatory involvement of other tissues including, e.g.,skin. Recently, a novel syndrome due to deficiency of interleukin-1 receptor antagonist (IL1RN), DIRA has been identified. Clinically the syndrome is characterized by neonatal onset of pustular dermatosis, periostitis and chronic sterile multifocal osteomyelitis, strongly resembling CNO. Homozygous mutations of IL1RN have been identified and resulted in a truncated protein that is not secreted, hence leaving the action of interleukin-1 unopposed. Methods Because of similar clinical, radiological and histological features of CNO and DIRA, we hypothesized that both disorders might share a common autoinflammatory process. Thus, we searched for the presence of mutations in the interleukin-1 receptor antagonist gene in 60 patients diagnosed with CNO. Results In one patient with chronic multifocal osteomyelitis a heterozygous missense variant: c.281G>T (p.Cys94Phe) was detected. In the other patients only frequent polymorphisms were found. Conclusion Our findings were not able to confirm mutations in IL1RN being an important contributing factor to the pathogenesis of CNO.

Juvenile Idiopathic Arthritis (JIA) is the most common cause of chronic arthritis in childhood and adolescents and encompasses a heterogeneous group of different diseases. Due to the promising results of B-cell depleting therapies in rheumatoid arthritis the role of B-cells in autoimmune diseases has to be discussed in a new context. Additionally, experiments in mouse models have shed new light on the antibody-independent role of B-cells in the development of autoimmune diseases. In this review we will discuss the importance of B-cells in the pathogenesis of JIA appraising the question for an immunological basis of B-cell targeted therapy in JIA.