Antibodies to CRMP3–4 associated with limbic encephalitis and thymoma

Abstract

SummaryWe present a case with subacute limbic encephalitis (LE) and thymoma. Neither classical onconeural antibodies nor antibodies to voltage gated potassium channels (VGKC) were detected, but the serum was positive for antiglutamic acid decarboxylase (GAD). The patient serum also stained synaptic boutons of pyramidal cells and nuclei of granule cells of rat hippocampus. The objective of the study was to identify new antibodies associated with LE. Screening a cDNA expression library identified collapsin response mediator protein 3 (CRMP3), a protein involved in neurite outgrowth. The serum also reacted with both CRMP3 and CRMP4 by Western blot. Similar binding pattern of hippocampal granule cells was obtained with the patient serum and rabbit anti-serum against CRMP1-4. The CRMP1-4 antibodies stained neuronal nuclei of a biopsy from the patient's temporal lobe, but CRMP1-4 expression in thymoma could only be detected by immunoblotting. Absorption studies with recombinant GAD failed to abolish the staining of the hippocampal granule cells. Our findings illustrate that CRMP3-4 antibodies can be associated with LE and thymoma. This has previously been associated with CRMP5.

Acute limbic encephalitis and glutamic acid decarboxylase antibodies: A reality?

“…Ten cases of LE with GAD-Ab have been described previously [3,7,8,[10][11][12][13]. However five of these also had other autoantibodies.…”

“…However, the prognosis of non-paraneoplastic immune-related LE is improved with immunotherapy [6]. Few patients have been described with LE and glutamic acid decarboxylase antibodies (GAD-Ab) [3,[7][8][9][10][11][12]. We report a case of immune-mediated LE associated with anti-GAD65-Ab that partially responded to immunotherapy.…”

Current approaches to the treatment of paraneoplastic encephalitis

“…The most frequently associated tumours are SCLC and thymoma, but a testicular tumour may also be detected, as reported by Kellinghaus and colleagues [Kellinghaus et al 2007]. Recently Knudsen and colleagues reported the case of a 52-yearold patient with subacute cognitive decline associated with thymoma harbouring abs directed against the collapsin response mediator protein types 3 and 4 (CRMP3 and CRMP4) [Knudsen et al 2007]. These proteins have 50% homology with the CRMP5.…”

Mapping CRMP3 domains involved in dendrite morphogenesis and voltage-gated calcium channel regulation

“…Regarding CRMP3, we first identified the protein as a target antigen of auto-antibodies present in some patients with cancer and autoimmune paraneoplastic neurological syndrome (Honnorat et al, 1999;Knudsen et al, 2007). CRMP3 expression was also found to be altered in Down syndrome (Weitzdoerfer et al, 2001).…”