Reibergram of intrathecal synthesis of C4 in patients with eosinophilic meningitis caused by Angiostrongylus cantonensis

Abstract

Angiostrongylus cantonensis produces eosinophilic meningitis in humans and is endemic in Thailand, Taiwan, China, and the Caribbean region. During infection with this parasite, it is important to know if the complement system may be activated by the classical or lectin pathway. Cerebrospinal fluid and serum samples from 20 patients with meningitic angiostrongyliasis were used to quantify C4 levels and albumin. Results were plotted on a C4 CSF/serum quotient diagram or Reibergram. Twelve patients showed intrathecal synthesis of C4. Antibody-dependent complement cytotoxicity should be considered as a possible mechanism that destroys third-stage larvae of this helminth in cerebrospinal fluid of affected patients.

Figure 1.

Quotient diagrams for C₄ (C₄ Reibergram), with data from patients infected with Angiostrongylus cantonensis. Reference ranges of blood-derived C₄ in cerebrospinal fluid are between the upper discrimination line (Qlim) and lower discrimination line. Upper hyperbolic line, Qlim, represents discrimination line between brain-derived and blood-derived C₄ fractions, in function of increasing QAlb. Values above Qlim indicate intrathecal fractions, which can be read from diagrams (dashed lines for intrathecal synthesis). Line Qlim represents 0% synthesis.

Figure 2.

Mechanisms involved in the immune response and C₄ intrathecal synthesis against Angiostrongylus cantonensis larvae invasion throughout the damaged blood-brain barrier (BBB). Larvae take advantage of existing factors such as metalloproteinases (MMPs) and adhesion molecules to enter the cerebrospinal fluid space. Antigen-presenting cells (APCs) are important in the innate response. C₄ can play an essential role by the interaction with mannose-binding lectin (MBL) or C₂ from the classical pathway. Complement component 2 bound to C_4b is cleaved by classical (C1s) or lectin (MASP2) proteases to produce C_4bC_2a.The final products of complement activation forming the membrane attack complex with the interaction of Th1 and Th2 mechanisms produce inflammation, necrosis, and apoptotic cells. Neurotoxins produced by eosinophils during the inflammation process including antibody production should be the most responsible for the central nervous system damage. This figure appears in color at www.ajtmh.org.