Studies in animal models suggest that complement activation is crucial in the pathogenesis of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Here we investigate the circulating complement activation profile of 66 patients with active stage AAV compared to that of 54 patients with AAV in remission. Plasma levels of C3a, C5a, soluble C5b-9, and Bb, all determined by enzyme-linked immunosorbent assay, were significantly higher in active stage than in remission of AAV, while plasma levels of properdin were significantly lower in the former than the latter disease stage. There was no significant difference in the plasma levels of C4d between active stage and remission. The plasma level of Bb in patients with active AAV significantly correlated with the proportion of total and cellular crescents in the renal biopsy, the erythrocyte sedimentation rate, and the Birmingham Vasculitis Activity Scores. Thus, systemic activation of complement by the alternative pathway takes place in human AAV. Circulating Bb might be a useful biomarker in assessing disease activity of AAV.

No abstract

SummaryBackground and objectives Previous study revealed that complement activation products of the alternative pathway could be detected in renal specimens of human ANCA-associated vasculitis. The current study aimed to investigate the clinical and pathologic significance of complement activation products in the urine and kidneys of patients with ANCA-associated vasculitis.Design, setting, participants, & measurements Renal biopsy specimens from 29 patients with ANCA-associated vasculitis diagnosed at Peking University First Hospital from January of 2008 to December of 2010 were randomly collected. Urine samples from 27 of 29 patients in active stage and 22 ANCA-associated vasculitis patients in complete remission who were independent of the above-mentioned 29 patients were collected. Urine samples from 28 patients with lupus nephritis and 25 healthy individuals were also collected. The renal deposition of Bb, C3d, and C5b-9 were detected by immunohistochemistry. The urinary levels of Bb, C3a, C5a, and soluble C5b-9 were determined by ELISA.Results The deposition, measured by the mean optical density of Bb, which is an alternative complement pathway marker, in glomeruli correlated with the proportion of total crescents (r=0.50, P=0.006), the extent of interstitial infiltrate (r=0.59, P=0.001), interstitial fibrosis (r=0.45, P=0.01), and tubular atrophy (r=0.55, P=0.002), whereas it correlated inversely with the proportion of normal glomeruli (r=20.49, P=0.008). The urinary levels of Bb, C3a, C5a, and soluble C5b-9 were all significantly higher in active compared with remission stage. The urinary levels of Bb in patients with active ANCA-associated vasculitis correlated with the serum creatinine (r=0.56, P=0.002) and correlated inversely with the proportion of normal glomeruli in renal specimens (r=20.49, P=0.009). ConclusionsThe present study provides additional evidence that complement activation through the alternative pathway occurred in the development of ANCA-associated vasculitis. The renal deposition of Bb and urinary Bb levels were associated with the severity of renal injury.

Testosterone (T) and vitamin D (VD) interact in androgen deficient men, however, this interaction and subsequent semen quality and bone mineral density (BMD) status is not clear in infertile men. Our objective was to investigate T, VD, semen quality, BMD and their relationships in Chinese infertile men. We conducted a cross-sectional study of 559 men aged 20-40 years, including 195 fertile men, 9 infertile men with known risk factors for osteoporosis (WR) and 355 infertile men without known risk factors for osteoporosis (WOR). WOR infertile men constituted 314 oligo-, astheno-, teratospermic or normospermic infertile men (OATN men) and 41 non-obstructive azoospermic men (NOA men). Differences of parameters were assessed, and the relationships were adjusted by multiple linear regression. WOR infertile men had significantly lower T, lumbar spine and total hip BMD than fertile men (all p < 0.05). Bioavailable T (Bio-T) and 25-hydroxyvitamin D [25(OH)D] were independent determinants of BMD in WOR infertile men (all p < 0.01) but not in fertile men. After stratifying Bio-T, WOR infertile men had lower BMD than fertile men (all p < 0.05) in low Bio-T subgroups (Bio-T ≤ 11.6 nmol/L), but not high Bio-T subgroups (Bio-T > 11.6 nmol/L). 25(OH)D was an independent determinant of sperm motility and morphology in WOR OATN men (all p < 0.05), with only borderline significance in fertile men(motility: p = 0.047; morphology: p = 0.056). T determined sperm concentration (square root) and morphology in WOR OATN men (all p < 0.001). No correlations between T and 25(OH)D were found in all groups. We suggest that infertile men have lower T and BMD than fertile men. 25(OH)D and T were associated with low BMD and poor semen quality in infertile men.