The complement system is a key component of innate immunity, responsible for mediating the rapid clearance of pathogens and coordinating adaptive immune responses. Although complement activation is essential for effective infection control and prevention, its excessive or dysregulated function contributes to the pathogenesis of various immune-mediated disorders. Therefore, therapeutic inhibition of the overactive complement cascade, in which specific components are selectively blocked to suppress pathological activation, plays an important role in the treatment of various complement (immune)-mediated diseases. This article provides an overview of complement inhibition as a therapeutic strategy, highlighting the infectious risks associated with its use. Disruption of complement-dependent host defence mechanisms increases the risk of invasive infections (caused by encapsulated pathogens, e.g., Neisseria spp., Streptococcus pneumoniae and Haemophilus influenzae type B), which represent a significant clinical challenge. Therefore, the use of complement inhibition should not only be effective but also safe in combination with the application of all possible tools to prevent infections. Strategies, such as vaccination and antibiotic prophylaxis, are crucial to minimise these complications, despite the persistence of the risk of breakthrough infections. Furthermore, this review examines advancements in patient risk stratification, evaluates alternative preventive measures, and identifies key gaps in current clinical practice. Future directions include improving monitoring protocols, creating more selective or locally acting complement inhibitors, and implementing biomarker-driven personalised therapies that maximise benefits while reducing side effects.

Familial Mediterranean fever (FMF) is the most common monogenic periodic fever syndrome among all monogenic autoinflammatory diseases. It is characterised by recurrent, self-limited fever attacks of short duration, polyserositis symptoms, and elevated acute-phase reactants. FMF has the highest prevalence in the Eastern Mediterranean region. The first descriptions of FMF cases in Central Europe date back to 2014. The prevalence in the Central European region was previously estimated at 1:465,500 in the paediatric population, with data on adult prevalence lacking. Patients with FMF who fulfilled Eurofever/PRINTO diagnostic criteria were included in the study. Massive parallel sequencing of clinical exome with evaluation of virtual panel for genes associated with inborn errors of immunity and autoinflammatory conditions was used in the vast majority of the patients. Statistical analysis of clinical and laboratory manifestation was performed. The prevalence of FMF in the Slovak population of the present study was 1:48,224 (1:41,348 in children and adolescents), which is significantly higher than expected. The most common variant in our cohort was M694V, present in 52.0% of alleles. Variant K695R was observed in 29.9% which is higher than reported in the other FMF cohorts. Abdominal pain and fever were the most prevalent clinical symptoms, although up to one-third of patients also experienced atypical symptoms such as tonsillitis or cervical lymphadenopathy. This paper provides the first comprehensive analysis of the Slovak National FMF cohort, including epidemiological data, clinical manifestations, and genetic background. Our data could contribute to the general knowledge about FMF characteristics in the underreported regions.

Background/Aims: Tumor necrosis factor receptor–associated periodic syndrome (TRAPS) is an autosomal dominant systemic autoinflammatory disease caused by mutations in the TNFRSF1A gene. The clinical presentation of TRAPS is heterogeneous, which can complicate its diagnosis. This study aimed to characterize the clinical and genetic features of patients with TRAPS diagnosed and treated in Slovakia, as well as to evaluate their therapeutic response to canakinumab. Materials and Methods: A retrospective analysis of clinical data from the Slovak national database of patients with periodic fever syndromes was performed, including 7 TRAPS patients diagnosed between 2019 and 2022 in Slovakia. These data were compared with findings from available cohorts from Europe, China, and Japan. Results: All 7 patients were female, with a median age at clinical disease onset of 6 years (range: 8 months to 30 years); 1 patient had adult-onset disease. The most frequent symptoms were recurrent episodes of fever (6/7), skin rash (6/7), arthralgia (6/7), myalgia (5/7), abdominal pain (4/7), chest pain (4/7), and general fatigue (4/7). Notably, 1 patient exhibited central nervous system (CNS) involvement manifesting as seizures and aseptic CNS inflammation. Genetic analysis identified 4 variants in TNFRSF1A, including the N145S variant (also referred to as N116S), a variant only rarely reported in the literature. Treatment with canakinumab resulted in a significant reduction in flare frequency and decreases in inflammatory markers. Conclusion: This study underscores the phenotypic diversity of TRAPS, as shown by the identification of the rare TNFRSF1A N145S variant and a case with CNS involvement. The estimated prevalence of TRAPS in Slovakia is approximately 1 : 780 000, and the clinical features of these patients are comparable to those reported in European cohorts. Furthermore, the favorable therapeutic response to canakinumab supports its potential as an effective treatment option for TRAPS.

X‐linked immunodeficiency with magnesium defect, Epstein–Barr virus (EBV) infection, and neoplasia (XMEN) is caused by a pathogenic variant in the magnesium transporter 1 ( MAGT1 ) gene. The defect leads to impaired N‐glycosylation which affects various immune processes. In this study, we described the disease course, clinical features and laboratory parameters observed in six patients from three families diagnosed with XMEN syndrome. They exhibit heterogeneous clinical manifestation while displaying typical laboratory signs of the disease, including decreased surface expression of NKG2D and CD28 on CD8 ⁺ T‐cells and NK cells, as well as defects in the N‐glycosylation of transferrin. We identified two novel variants in the cohort: a frameshift variant c.444dup in exon 3, and a splicing variant c.998‐20_1008del. Notably, a patient with the c.444dup variant presented with severe autoimmune cytopenia as an isolated manifestation of the disease, while his younger brother, carrying the same variant, exhibited predominantly mild skin infections. These findings illustrate varying degrees of severity in penetrance and highlight that some patients may exhibit only partial symptoms. Furthermore, our study confirmed defects in perforin expression in XMEN syndrome. We observed a significant reduction in perforin expression within CD8 ⁺ T‐cells and NK cells which may lead to increased susceptibility to recurrent infections and autoimmune complications frequently observed in XMEN patients.

Background: VEXAS syndrome is an autoinflammatory syndrome caused by pathogenic somatic mutations in the UBA1 gene in hematopoietic stem cells. Although the disease predominantly affects men over 50 years of age, women can also be affected. Clinically, VEXAS syndrome manifests with inflammatory and hematologic findings, including: recurrent fever, skin lesions, pulmonary infiltrates, recurrent ear chondritis, arthritis, and unprovoked venous thrombosis. Hematological involvement also includes macrocytic anaemia, myelodysplastic syndrome, thrombocytopenia, monoclonal gammopathy and the presence of vacuoles in myeloid and erythroid precursor cells. Objectives: We present the first confirmed case of VEXAS syndrome in Slovakia. Methods: A retrospective analysis of clinical data related to a patient diagnosed with VEXAS syndrome at the National Centre for Periodic Fever Syndromes is provided. Results: A 66-year-old male patient presented with recurrent episodes of fever, weakness, cough, dyspnea, ear chondritis, migratory arthritis, and recurrent deep venous thrombosis. Molecular genetic testing using massive parallel whole exome sequencing identified a likely pathogenic variant, p.Met41Leu, in the UBA1 gene, previously reported to be associated with VEXAS syndrome. Conclusion: We describe the first clinical case of VEXAS syndrome in the Slovak Republic. Clinical phenotypes, as well as therapeutic outcomes are discussed. The aim of this case report is to raise awareness of VEXAS syndrome, as based on the available literature, it seems that a significant number of patients with VEXAS in Slovakia remain undiagnosed.