The use of AQP4-antibody testing in diagnosis Thai patients with neuromyelitis optica

Background: There are several methods to detect AQP4-antibody which is essential for diagnosis neuromyelitis optica (NMO). Objective: To evaluate an accuracy of the commercially available kit compared with other available tests. Methods: One hundred and twelve patients who visited the multiple sclerosis (MS) clinic at Siriraj Hospital were tested for AQP4-antibody by cell-based assay with Sendai method (Postfix-CBA), a commercial kit (Prefix-CBA) and an indirect immunofluorescence tissue-based assay (IIF-TBA). The patients were classified to NMO, seropositive NMOSD (AQP4-pos NMOSD), seronegative NMOSD (AQP4-neg NMOSD), classic MS (CMS), atypical MS and clinical isolated syndrome (CIS). Results: Based on postfix-CBA, there were 26 NMO, 25 AQP4-pos NMOSD, 19 AQP4-neg NMOSD, 34 CMS, 4 atypical MS and 14 CIS. There were 5 (1 NMO, 2 AQP4-neg NMOSD, 2 CMS), 7 (1 NMO, 6 AQP4-pos NMOSD) and 2 patients (1 AQP4-neg NMOSD, 1 CIS) were seropositive only by CBA-kit, CBA-Sendai and IIF-TBA respectively. Sixteen patients were seropositive by both CBA but negative by IIF-TBA. Both CBA showed strong correlation. Conclusions: CBA-kit is a relatively sensitive, comparable assay to detect anti-AQP4 antibody in Thai NMO patients. Since the kit may have a few false-negative and false-positive results, a more sensitive assay is necessary for a much more proper diagnosis in the future. Neurology Asia 2014; 19(4) : 375 – 385 Address correspondence to: Naraporn Prayoonwiwat, MD, MS Clinic, Siriraj Hospital, Mahidol University. 2 Prannok Road, Bangkoknoi, Bangkok, Thailand 10700. Tel: 66-2-4197101, Fax: 66-2-4122400, Email: [email protected] INTROUDUCTION Neuromyelitis optica (NMO) is an immunemediated CNS disease typically affecting the optic nerve and spinal cord. Since the discovery of serum NMO-IgG antibody in patients with NMO in 2004, a number of unexpected cases have been increasingly seen. In the original study, Lennon et al. detected NMO-IgG antibody from 45 North American patients with NMO and 12 Japanese patients with the opticospinal type of multiple sclerosis (OSMS). The sensitivity and specificity was reported to be 73% and 91% for NMO, and 58% and 100% for OSMS. In 2005, Lennon et al. found that NMO-IgG binds to aquaporin-4 (AQP4) water channel expressed on astrocyte foot processes lining the blood bran barrier in grey matter of spinal cord, periventricular and periaqueductal areas. Detection of serum AQP4antibody is now one of the supportive criteria for NMO diagnosis. It not only serves as a disease marker but also plays a crucial role in the pathogenesis of NMO. Several methods available for AQP4-antibody detection include the original indirect immunofluorescence tissue-based assay (IIF-TBA), enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence cell-based assay (IIF-CBA) with differences in sensitivity and specificity. Recent studies indicate that CBA is the most sensitive assay for detecting AQP4antibody. Previous reports have shown high prevalence of NMO in Asia, especially Thailand, and they were problematic when diagnosing based on clinical manifestations only. However the sensitive CBA done by Tohoku University or Oxford University are difficult to conduct in Thailand and therefore, widely available testing kits with high sensitivity and specificity has replaced it. The primary objective of the study is to evaluate the accuracy of the commercially available kit to diagnose Thai patients with NMO/ NMOSDs using a large Thai cohort which has a high prevalence of NMO/NMOSD.