Anti-AQP4 antibodies tied to earlier NMOSD onset, more relapses
Antibody-positive patients more likely to have other autoimmune diseases
People with neuromyelitis optica spectrum disorder (NMOSD) who test positive for self-reactive antibodies against the aquaporin 4 (AQP4) protein are more likely to be women, and have an earlier disease onset and more relapses than those who test negative.
That’s according a single-center study in Argentina that also showed that those who test positive for the antibodies were significantly more likely to have other autoimmune diseases.
“Distinct clinical course patterns have been identified” between NMOSD patients with or without anti-AQP4 antibodies, the researchers wrote. The study, “Distinct clinical patterns in AQP4-IgG- positive NMOSD patients vs. Seronegative: Insights from a single-center study in Argentina,” was published in Multiple Sclerosis and Related Disorders.
NMOSD is an autoimmune disease marked by damaging inflammation in the nerves of the eyes and spinal cord. Most cases are associated with the production of self-reactive antibodies that target AQP4, a protein on nervous system support cells called astrocytes.
“However, a subset of patients remains [negative for anti-AQP4 antibodies], lacking a definitive diagnostic biomarker,” the researchers wrote, noting that previous studies have found clinical course differences between antibody-positive and antibody-negative patients.
Differences between anti-AQP4 antibody-positive, -negative patients
Here, researchers sought to identify potential differences between the groups by analyzing data from 94 NMOSD patients (83% females) followed at a single center in Buenos Aires from January 2005 through December 2023. The patients’ median age was 31 (range, 2-68) at the onset of symptoms and 44 (range, 17-74) at the time of the study.
Seventy-seven patients (82%) tested positive for anti-AQP4 antibodies while the remaining 17 (18%) tested negative. In the antibody-positive group, there were 10 women for every man, while the antibody-negative group had almost the same number of women and men, a statistically significant difference.
The female-to-male ratio among patients with anti-AQP4 antibodies showed “a significant deviation toward a female predominance,” the researchers wrote.
While the median age at symptom onset was generally comparable between the groups, a greater proportion of antibody-positive patients developed symptoms in early adulthood (before age 50) than those without the antibodies (81% vs. 35%). Among the subgroup with early-adult onset, a significantly greater proportion tested positive for anti-AQP4 antibodies (91% vs. 9%).
The antibody-positive group was also significantly more likely to have relapses, when symptoms suddenly worsen or new ones appear, during follow-up than those without the antibodies (99% vs. 17.6%). These findings suggest NMOSD is more aggressive in those who test positive for the antibodies.
Also, a significantly greater proportion of patients with anti-AQP4 antibodies had other autoimmune diseases (44% vs. 12%). Autoimmune thyroid disease was present in 25.6% of antibody-positive patients, but in none without the antibodies.
Treatment choices also varied between the groups. Antibody-based therapies, including rituximab (sold as Rituxan and others), Soliris (eculizumab), and Enspryng (satralizumab-mwge), were the most common medications among positive-testing patients. The antibody-negative group was most often given nonselective immunosuppressive treatments.
Data from the “the largest cohort of patients with NMOSD under follow-up in Buenos Aires, Argentina” showed “female predominance, [early adult-onset-NMOSD], recurrence course, and a high prevalence of autoimmune disease in [anti-AQP4 antibody-positive] patients,” the researchers wrote, noting it suggests “a more pronounced autoimmunity profile.”
About the Author
