The phenotypes of complement C4 were determined by agarose gel electrophoresis in 130 patients with end-stage renal failure of various causes and compared with those of 140 healthy controls. C4 allotype frequencies did not differ between patients and controls. Null alleles of both isotypes C4A and C4B were increased, but also without reaching significance. In type 1 diabetics an increased frequency of C4AQ0 (25 vs. 11.8%, p < 0.05) was found. Patients with two null alleles were far more frequent in the group with insulin-dependent diabetes mellitus (25 vs. 3.6%, p < 0.01). We confirmed the presence of a previously described uremic variant of C4B1. Additional uremic variants of C4 were detected in uremic patients homozygous for C4A3, B2 and B3. The relative electrophoretic migration values of the uremic variants of C4A3, Bl, B2 and B3 were 132.1 ± 2.9,35.8 ± 1.5,70.4 and 73.9. These variants appear early in the course of chronic renal failure and disappear after successful renal transplantation. Uremic variants are the only acquired C4 phenotypes known so far. How uremia causes these variants remains unclear, but probably involves carbamylation of the C4 molecule.

Behçet’s disease (BD) can affect the genital system and is more common in Middle Eastern countries and Asia but also occurs in Caucasian people. Aim of this study was to evaluate the prevalence of sexual dysfunction (SD) and depression in patients with BD compared to a healthy control group (HCG). In addition, differences with regard to depression and patients’ origin were evaluated. This prospective, monocentric study included 106 consecutive patients from our specialized BD outpatient clinic. Patients were asked to fill out the paper based standardized and validated questionnaires International Index of Erectile Function (IIEF), the Female Sexual Function Index (FSFI) and the Beck Depression Inventory (BDI). In addition, 206 healthy controls were asked to fill out the questionnaires. 106 patients with BD were evaluated and 206 participants in the HCG. The mean age in BD group was 40.5 years as compared to 44.4 years in the HCG. Half of the patients had Middle Eastern and half Caucasian origin. SD was found in 24.5% of all subjects. Only 6.9% of male patients showed signs of SD, while half of the women’s group was suffering from SD. The prevalence for SD was significantly higher in women with Middle Eastern ethnic origin compared to women with Caucasian origin (75 vs. 33.3%, p = 0.024). Erectile Dysfunction occurred in 55% of all male patients which was not statistical different from the HCG. Genital ulcers affected 73.6% of all patients. Depression was found in 36.7% of all subjects as compared to 6.25% in the HCG (p < 0.001). Both, SD and depression correlated positively in males (p = 0.017) and females (p = 0.013). SD and depression are very common problems in BD and should be addressed by the treating physician. Both manifestations are intensifying each other. Depression especially is more prevalent compared to the healthy population.

The most likely but still hypothetical explanation for predominance in glomerular deposition of C4A over C4B in many cases of immune complex-mediated glomerulonephritis is the greater affinity of C4A to protein-containing immune complexes as compared to C4B.

Acne inversa (AI) patients present with painful and disabling cutaneous nodules, abscesses, fistulae and extensive scarring, typically situated within the large humid skin folds of the axillary, inguinal, perianal and/or submammary areas. In addition, AI patients frequently suffer from metabolic, endocrinological, and psychological morbidities. The high burden of patients contrasts with the fragmentary understanding of underlying pathogenetic processes and the lack of biomarkers reflecting the inflammatory state. To illuminate this issue we individually quantified the levels of 40 parameters in the blood of AI patients including proteins and microRNAs. These analyses revealed lipocalin-2 (LCN2) to be most significantly upregulated. Regarding the cellular sources, we demonstrated that neutrophilic granulocytes, abundant in AI lesions, secreted LCN2 especially after TNFa stimulation. Furthermore, LCN2 production was evident for keratinocytes in response to TNFa with amplifying contribution of IL-17A, but not for fibroblasts or endothelial cells. Accordingly, LCN2 levels positively correlated with systemic TNFa levels in AI. LCN2 blood levels also positively correlated with the disease severity. In-depth analyses revealed a link between LCN2 blood levels and the number of regions with inflammatory nodes and fistulas, but not with the number of scars. Functionally, we found evidences for a role of LCN2 in cardiovascular alterations as deduced from the correlation between LCN2 and both resistin and chemerin blood levels. In summary, we demonstrate elevated LCN2 levels in skin lesions and blood of AI patients, shed light on their cellular sources, suggest their role in metabolic comorbidities, and recommend LCN2 as blood biomarker for AI disease activity.

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