Although the biological function of mCRP entails activation of the classical complement pathway [62], disruption of the alternative complement pathway [17], facilitation of opsonization [63], and activation of endothelial cells [17], in our hands, the levels of mCRP did not correlate significantly with the levels of complement proteins (C3, C4, or C3d). When planning this study, we initially hypothesized that the mCRP/pCRP ratio could reflect disease activity or clinical features in SLE. Characteristics and descriptive data for patients with systemic lupus erythematosus (SLE) and ANCA-associated EIF4EBP1 vasculitis (AAV) (%)139 (87)14 (47)Ongoing pharmacotherapy?Glucocorticoids, (%)110 (69)22 (73)?Methotrexate, (%)18 (11)2 (7)?Mycophenolate mofetil, (%)22 (14)1 (3)?Rituximab, (%)9 (6)7 (23)?Hydroxychloroquine, (%)103 (64)0 (0)?Other immunosuppressants, (%)21 (13)0 (0)Disease variables?Disease duration, years (mean (SD))21 (11)0.77 (3.8)?SLEDAI-2K (median (IQR))4 (1C8)C?SDI (median (IQR))1 (0C2)C?Birmingham Vasculitis Activity Score (median (IQR))C14 (12C18)?Microscopic polyangiitis, (%)C14 (47)?Granulomatosis with polyangiitis, (%)C16 (53)?New-onset ((%)(%; ref? ?20)40 (25)C?MPO-ANCA, IU/mL (median (IQR))C0.6 (0.3C55)?MPO-ANCA positive, (%; ref? ?3.5)C14 (47)?PR3-ANCA, IU/mL (median (IQR))C9.8 (0.3C70)?PR3-ANCA positive, (%; ref? ?2)C16 (53)?aAnemia, (%)36 (23)26 (87%)?Hematuria, (%)47 (30; (%)29 (18; (%)59 (37)C?2. Discoid rash, (%)29 (18)C?3. Photosensitivity, (%)87 (54)C?4. Oral ulcers, (%)17 (11)C?5. Arthritis, (%)129 (81)C?6. Serositis, (%)58 (36)C?7. Renal disorder, (%)45 (28)C?8. Neurologic disorder, (%)11 (7)C?9. Hematologic disorder, (%)97 (61)C?10. Immunologic disorder, (%)91 (57)C?11. IF-ANA, (%)157 (98)C Open in a separate window tests or Eribulin Mesylate KruskalCWallis test. nonparametric correlation analyses were performed using Spearmans rank correlation coefficient test. For comparisons between groups with paired data, Wilcoxon signed rank tests were used. For comparisons between binary data, exact em /em 2-test was carried out. Undetectable levels of mCRP were set to half the level of the detection limit (1.25?g/L). A em p /em -value of??0.05 was considered statistically significant. Results pCRP and mCRP The median value (with IQR) for the levels of pCRP and mCRP in patients with SLE were 2.8?mg/L (1.3C8.7) Eribulin Mesylate and 0.0037?mg/L (0.0013C0.0074) respectively, and 26?mg/L (7.1C118) and 0.011?mg/L (0.0058C0.022) for AAV (Fig.?1). The levels of mCRP and pCRP did not correlate significantly with each other in either SLE (rho?=????0.002, em p /em ?=?0.98) or AAV (rho?=?0.30, em p /em ?=?0.11). Open in a separate window Fig. 1 The graphs show serum levels of pentameric C-reactive protein (pCRP; A) and monomeric CRP (mCRP; B), as well as in mCRP/pCRP ratios (C) in systemic lupus erythematosus (SLE; em n /em ?=?160) and ANCA-associated vasculitis (AAV; em n /em ?=?30). Panel D illustrates levels of autoantibodies against complement protein 1q (anti-C1q) in SLE as well as in healthy controls (HC; em n /em ?=?100). In addition, panel B includes a group of healthy controls (HC; em n /em ?=?39; B). The dotted line represents CRP cut-off level applied for cardiovascular risk assessment in clinical routine (2.0?mg/L; A) (*?=? em p /em ??0.05, ***?=? em p /em ? ?0.001) The subjects with SLE had lower levels of both CRP forms than the AAV patients ( Eribulin Mesylate em p /em ? ?0.001 for both comparisons). In addition, the ratio of mCRP/pCRP showed a significant difference between SLE and AAV ( em p /em ? ?0.01; Fig.?1), with mCRP/pCRP ratios showing median values (IQR) 3.7??10?3 (1.3??10?3C7.4??10?3) vs. 4.3??10?4 (1.2??10?4C1.2??10?3). CRP in SLE Among the 160 SLE cases, 65 (41%) had active disease (SLEDAI-2K??5) whereas 95 (59%) were in a quiescent phase of their disease. For paired samples, the ratios of mCRP/pCRP were lower in samples obtained from active compared to non-active disease ( em p /em ??0.05). However, this comparison did not reach statistical significance in the cross-sectional cohort when samples were divided into active and non-active disease ( em p /em ?=?0.14). No significant differences were found regarding the levels of pCRP or mCRP between active disease and non-active disease neither for the paired nor the cross-sectional samples (Fig.?2). Open in a separate window Fig. 2 Levels of pCRP (A, D) and mCRP (B, E) and ratios of mCRP/pCRP (C, F) between active and non-active systemic lupus erythematosus. Panels A, B, and C are based on 160 non-paired patient samples whereas D, E, and F represent paired samples from 22 patients (*?=? em p /em ??0.05) Patients with normal and abnormal/subnormal levels of ESR, C3, and C4 based on reference intervals were separated into groups, and the levels of pCRP and mCRP as well as the Eribulin Mesylate ratios of mCRP/pCRP in each group were compared (Fig.?3). No significant differences were found for patients with normal or subnormal levels of C3 or C4. However, a highly significant difference ( em p /em ? ?0.001) was observed for both pCRP and the mCRP/pCRP ratios for patients with normal Eribulin Mesylate vs. abnormal ESR. Open in a separate window Fig. 3 Comparisons of pCRP (ACD), mCRP (ECH), and mCRP/pCRP ratios (ICL) demonstrated between deviating levels of erythrocyte sedimentation rate (ESR), complement protein 3 (C3), C4, and negative/positive anti-C1q autoantibody.