Background/Purpose: Activation of the classical complement (C) pathway by immune complexes is a characteristic of patients with systemic lupus erythematosus (SLE). Accelerated consumption outstrips synthesis and is the cause of the hypocomplementemia found in the disease. However, a complete characterization of the three pathways (classical -CL-, alternative -AL- and lectin -MBL-) of the C system has not been performed in patients with SLE. In the present work we aim to assess the function of the 3 pathways of C system through both functional assays and the measurement of individual serum components. We then study how full C characterization is related to disease expression.

Methods: New generation functional assays of the three pathways of the C system were performed in 284 patients with SLE (in these ELISA assays the amount of complement activation is expressed in a qualitative way relative to the value of a positive control). Activation of the 3 pathways was defined if its value was below 2 standard deviation of reference values. The concordance of this new generation assays with haemolytic complement (CH50) activity of serum was studied trough the Passing-Bablok method. Additionally, serum levels of C2, C3, C4, C3a, C1q and C1-inhibitor, and factors H and D, were assessed. Patients with SLE were fully characterized including demographics, disease activity (SLEDAI), severity (Katz index) and damage (SLICC) scores, and treatments used in the disease. Multivariable regression analysis was performed to describe the relation of C system to disease patterns and manifestations.

Results: Average CH50 was 44 ± 22 U/ml and it agreed with CL pathway through ELISA. All C pathways were found to be activated compared to reference values: CL (91 ± 38 vs. reference 99 ± 80, p=0.026), AL (47 ± 38 vs 71 ± 21 %, p< 0.001) and MBL (30 ± 42 vs 49 ± 21, p< 0.001). When pathway activation was defined as a binary value according to reference cut-offs, 53% of the patients were found to have no activation of either pathway. Contrary, 18% of the patients had a patter consisting in normal CL, low AL, normal MBL (that ontologically corresponds to a deficiency/activation of properdin or factors B and D); 18% had low CL, low AL, normal MBL; and 6% low CL and normal AL and MBL (deficit of C1q, C1r or C1s). Individual C components analysis confirmed these patterns being lower according to the deficiency/activation of the pattern. SLEDAI and SLICC, but not Katz, were significant associated with lower values of the CL and AL pathways (this was not the case for MBL). Disease activity (SLEDAI >=1) was associated with having a C pattern consisting in low CL and AL and normal MBL (OR 2.52, 95CI 1.28-4.96, p=0.008); this relation was not found with other C deficiency/activation patterns. Besides, although SLICC score correlated with CL and AL pathways, no association was found between this score and any C pattern.

Conclusion: At least, 50% of SLE patients showed activation of the C. All three C pathways showed consumption compared to reference values. The most frequent patterns of activation consist in normal CL, low AL, normal MBL; and low CL and AL, normal MBL. Disease activity, but not damage, was associated with only the pattern of deficiency/activation represented by low CL and AL, and normal MBL.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/full-characterization-of-the-three-pathways-of-complement-system-in-patients-with-systemic-lupus-erythematosus-relation-to-disease-expression/