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Complement levels and risk of organ involvement in patients with systemic lupus erythematosus
Ignacio Javier Gandino1, Marina Scolnik1, Emmanuel Bertiller1
1Hospital Italiano de Buenos Aires, Rheumatology Section, Medical Services. Instituto Universitario Hospital Italiano de Buenos Aires, and Fundacion PM Catoggio., Buenos Aires, Argentina.
Insights
Systemic lupus erythematosus (SLE) patients with fluctuating complement levels show higher rates of kidney damage. However, neither persistently low nor fluctuating complement levels are associated with increased mortality or visceral damage in SLE patients.
Area of Science:
- Rheumatology
- Immunology
- Clinical Medicine
Background:
- Complement system activation is implicated in Systemic Lupus Erythematosus (SLE) pathogenesis.
- Complement levels (C3, C4) correlate with disease activity and organ damage in SLE.
- Understanding complement behavior patterns is crucial for predicting SLE clinical outcomes.
Purpose of the Study:
- To investigate the association between complement behavior patterns and clinical manifestations in SLE patients.
- To determine the relationship between complement levels and visceral injury, including lupus glomerulonephritis.
- To evaluate the impact of complement behavior on mortality in SLE.
Main Methods:
- Analysis of C3 and C4 levels in SLE patients (ACR/SLICC criteria) from 2000-2013.
- Categorization of patients into groups: persistent low complement, normal complement, and fluctuant complement levels.
- Comparison of clinical characteristics, organ damage (SLICC/ACR), and mortality across complement groups.
Main Results:
- Fluctuant complement levels were associated with a higher frequency of lupus glomerulonephritis (75%).
- Normal complement levels correlated with lower prevalence of hematologic involvement and anti-dsDNA antibodies.
- No significant differences in accumulated damage or 10-year survival rates were observed between complement groups.
Conclusions:
- Patients with constant normal complement have a lower prevalence of hematologic involvement and anti-dsDNA antibodies.
- Fluctuant complement levels in SLE patients are linked to increased renal impairment.
- Neither persistent low nor fluctuant complement levels predict increased mortality or visceral damage in SLE.
Objective:
Complement plays a major role in SLE. Complement participation has been linked to disease activity and damage. Our objective was to estimate the association of complement behaviour with clinical manifestations, visceral injury and mortality in patients with SLE.
Methods:
Complement determinations (C3 and C4 levels) were analysed in patients with SLE (fulfilling American College of Rheumatology (ACR) or Systemic Lupus International Collaborating Clinics (SLICC)criteria) seen at a university hospital between 2000 and 2013. Patients were grouped in those with permanent C3 and/or C4 low values (low complement group), those with C3 and C4 constant normal values (normal complement group) and those with fluctuant values (periods of normal and periods of low values: fluctuant group). Clinical characteristics and mortality were analysed and compared between groups.
Results:
270 patients with SLE were included (242 females, 89.6%), mean age at diagnosis was 34.2 years (SD 15.8). 75 patients had fluctuant levels of complement, 79 patients had persistent low complement levels and 116 had normal complement levels. Lupus glomerulonephritis was more frequent in patients with fluctuant levels (75%, 56% and 49%, respectively, p=0002). The normal complement group had less frequency of haematological involvement and anti-double stranded DNA (dsDNA) antibodies. At the end of the follow-up, 53% of the patients had damage (SLICC/ACR ≥1). In a Cox proportional hazard model age at diagnosis, neurological impairment, thrombocytopaenia and corticosteroids were associated with more damage, while hydroxychloroquine was a protective factor. There were no differences between complements groups on accumulated damage. Ten-year survival rate was 93%, 93.5% and 92% for the normal complement group, the persistently low group and the fluctuant group, respectively.
Conclusions:
Patients with constant normal complement had lower prevalence of haematological involvement and anti-dsDNA, while patients with fluctuant complement had higher renal impairment. Neither the persistent low complement nor the fluctuant complement groups had increased mortality and/or visceral damage.
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