Anti-IL6 Autoantibodies in an Infant With CRP-Less Septic Shock

Abstract

Background: Interleukin-6 (IL-6) is a pleiotropic cytokine with a multitude of pro-inflammatory effects. Serum C-reactive protein (CRP) is an acute phase protein induced mainly by IL-6 in response to inflammatory conditions, particularly infection. The biological functions of CRP include opsonisation, induction of phagocytosis, complement activation, or chemotaxis enhancement. Factors interfering with IL-6-mediated recruitment of innate immune responses, such as the presence of anti-IL6 antibodies, may therefore compromise the host resistance to microbial pathogens. This has major implications for the use of IL-6-targeting biologics, such as tocilizumab or sarilumab in rheumatologic, immune dysregulation diseases, and cancer. Case presentation: 20-month-old Czech female developed severe septic shock with clinical and laboratory signs of systemic inflammation but no increase of CRP or IL-6. The offending pathogen was most likely Staphylococcus aureus, detected in a throat swab; the response to antibiotic treatment was prompt. A defect in the integrity of IL-6/CRP axis was suspected and verified by the detection of neutralizing IL-6 antibodies in the serum of the child. Conclusion: We report a first case of systemic bacterial infection in a patient with anti-IL6 autoantibodies. Disturbed IL-6 signaling, whether iatrogenic by targeted IL-6 blockade or endogenous due to the presence of autoantibodies against IL-6, represents a risk factor for increased infectious susceptibility. Patients with severe bacterial infection without elevation of CRP should be examined for the presence of anti-IL6 autoantibodies.