214. Utility of serum complement factors C3 and C4 as biomarkers in Giant Cell Arteritis
Creators: name: Edoardo Conticini1, 2
name: Hellmich1, Bernhard
name: Fredian, Bruno
name: Csernok1, Elena
name: Christian Löffler1, 3
Publisher: name: Zenodo
Year: 2022
Subjects: Vasculitis
ANCA
Abstracts
Giant Cell Arthritis
MPA
GPA
EGPA
Takayasu
IgA vasculitis

description: <strong>Background:</strong> There is a strong unmet need for novel biomarkers in Giant Cell Arteritis (GCA): C-reactive protein (CRP) may be unreliable in case of patients treated with Tocilizumab (TCZ). Several molecules have been proposed, but, to date, none of them has provided sufficiently robust evidence to be used in clinical practice. In this regard, we aimed to assess whether serum complement factors, whose activation has a paramount role in several autoimmune diseases, may be considered a useful biomarker in GCA. <strong>Methods: </strong>We retrospectively enrolled all GCA patients from our vasculitis center who underwent C3 and C4 measurement at baseline. All patients were evaluated at 3, 6, 12 and 24 months after first diagnosis, as part of routine follow-up visits. Two assessments after the end of the observational period, in case of further relapses, were also included. <strong>Results:</strong> One-hundred and thirty-nine consecutive patients were enrolled. At baseline, mean serum levels of C3 and C4 were within the normal range. Both C3 and C4 values decreased significantly between baseline and the first follow-up evaluation at remission (Table 1). C4 levels showed a stronger predictability for the state of disease compared to C3 using a binary multivariate regression model (C4: ß coefficient 0.71, p=0.005, C3: ß coefficient 0.009, p=0.141). When patients were stratified according to disease activity, C3 and C4 appeared significantly reduced in patients in remission (107.07±19.86; p=0.0006 and 19.86±10.27; p=0.01, respectively) and sustained remission (95.85±18.04, p=0.001; and 15.61±9.75; p=0.006). Moreover, there was a statistically non-significant trend towards lower C3 and C4 serum levels in patients with sustained remission and GC-free remission compared to patients who had a shorter duration of remission and/or needed higher GC doses. In patients in remission, CRP levels correlated strongly with C3 and C4. A correlation of CRP with C3 was also found in active patients at baseline, while C4 levels were not associated with CRP at baseline and at relapse. In a binary regression model CRP and ESR showed significantly stronger association with the state of disease than C3 and C4. Among the patients who relapsed, a statistically significant difference with remission findings was evidenced for CRP, ESR and C3, but not for C4. In patients treated with TCZ, serum levels of C3 and C4 were statistically significantly decreased compared to baseline. No significant correlation was found between C3 and CRP (r=-0.04, p&lt;0.9), and C4 and CRP (r=0.4, p=0.28). No significant association was found between C3 and C4 and imaging findings. <strong>Conclusions: </strong>Serum C3 and C4 do not seem to provide any added value in the diagnosis of GCA, as normal values do not rule out active vasculitis. However, serum levels of C3 and C4 correlate with disease activity. In patients treated with TCZ, C3 and particularly C4 levels are even lower than in the ones on treatment with other immunosuppressants. As the low C4 complement levels found in TCZ-treated patients are not correlated with CRP-levels, C4 should be further evaluated as a potential biomarker in TCZ-treated patients, in whom CRP may be unreliable. Preliminary data<sup>1</sup> have displayed that C4 may increase in refractory or relapsing patients treated with TCZ: this may suggest that the reduction of C4 is related to disease activity and not only to the pharmacological inhibition of IL-6, confirming its potential reliability in such patients. <strong>Disclosures: </strong>None. <strong>Table 1. </strong>Markers of inflammation and complement factors in different stages of disease Baseline (T0) Remission <em>p</em> value CRP (mg/l) 52.1±41.3 8.41±11.5 &lt;0.00001** ESR (mm/h) 57.6±32.4 16.7±15.4 &lt;0.00001** C3 (mg/dl) 133.0±29.0 107.1±27.1 0.0006** C4 (mg/dl) 25.9±9.0 19.9±10.3 0.01* All remissions Relapse <em>p</em> value CRP (mg/l) 8.4±11.5 21.4±28.0 0.02* ESR (mm/h) 16.7±15.4 28.3±23.6 0.035* C3 (mg/dl) 107.1±27.1 122.8±16.7 0.031* C4 (mg/dl) 19.9±10.3 27.3±9.1 0.07 Before TCZ During TCZ <em>p</em> value CRP (mg/l) 44.9±33.1 0.4±0.7 0.00042** ESR (mm/h) 42.9±36.1 5.0±5.2 0.003** C3 (mg/dl) 129.4±32.8 83.1±19.7 0.001** C4 (mg/dl) 21.9±7.2 8.3±3.8 0.000069** List of abbreviations: CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; TCZ: Tocilizumab; *<em>p</em>&lt;0.05; **<em>p</em>&lt;0.01 (Student T-test).