From the Guidelines
Patients with low C3 and C8 complement levels should generally avoid methotrexate (MTX) unless specifically directed by their healthcare provider, as it may increase the risk of infections and worsen immune system abnormalities. Complement deficiencies indicate immune system abnormalities that may increase infection risk, and MTX, being an immunosuppressant, could potentially worsen this vulnerability 1. If MTX is deemed necessary for conditions like rheumatoid arthritis or psoriasis, careful monitoring is essential with regular blood tests to check complement levels, complete blood counts, and liver and kidney function 1. Prophylactic antibiotics might be considered alongside MTX therapy to prevent infections. The decision to use MTX should be individualized based on the underlying cause of complement deficiency, the severity of the condition requiring MTX, and the patient's overall health status.
Some key considerations for MTX use include:
- Starting with a low dose and gradually increasing as needed and tolerated 1
- Monitoring liver and kidney function, as well as complete blood counts, regularly 1
- Considering alternative treatments, such as biologics, which may have a more favorable safety profile in patients with complement deficiencies 1
- Weighing the potential benefits of MTX against the potential risks, including increased infection risk and worsening of immune system abnormalities.
The immunosuppressive effects of MTX work by inhibiting dihydrofolate reductase and reducing inflammatory cytokines, which could theoretically further compromise an already challenged immune system in patients with complement deficiencies 1. Therefore, MTX should only be used in patients with low C3 and C8 complement levels under close supervision and with careful consideration of the potential risks and benefits.
From the Research
Complement System and Low C3 and C8 Cells
- The complement system plays a crucial role in both innate and acquired immune responses, and deficiencies in any of its components can lead to increased susceptibility to infections and autoimmune diseases 2, 3.
- Low levels of complement C3 have been associated with poor prognosis in patients with renal ANCA-associated vasculitis, and have been linked to worse long-term patient and renal survival 4.
- C3 inhibition has been shown to be safe in non-human primates, with no increased susceptibility to infections or weakened immune system observed after prolonged treatment with a C3 inhibitor 5.
- In autoimmune hemolytic anemia patients, low serum C3 levels have been observed, and serum C4 levels have been found to be negatively correlated with cold agglutinin test and direct antiglobulin test titers 6.
Methotrexate (MTX) Treatment
- There is no direct evidence in the provided studies to suggest that patients with low C3 and C8 cells should take MTX.
- However, MTX is an immunosuppressive medication that is often used to treat autoimmune diseases, and its use may be considered in patients with low C3 and C8 cells who are at risk of developing autoimmune diseases or infections.
- The decision to use MTX in patients with low C3 and C8 cells should be made on a case-by-case basis, taking into account the individual patient's medical history, laboratory results, and overall health status.
Key Findings
- Low C3 levels are associated with poor prognosis in patients with renal ANCA-associated vasculitis 4.
- C3 inhibition is safe in non-human primates, with no increased susceptibility to infections or weakened immune system observed 5.
- Autoimmune hemolytic anemia patients have reduced serum C3 levels, and serum C4 levels are negatively correlated with cold agglutinin test and direct antiglobulin test titers 6.