Central Nervous System-Specific Autoantibodies Testing in Immune-Mediated Disorders: How They Affect Treatment Decisions?

To the Editor

We read with great interest the recently published article titled “Influence of Autoimmune Antibody Testing on the Use of Immunotherapy on an Inpatient Neurology Service” by Galetta et al. ¹ The authors have concluded that the results of antibody testing did not influence inpatient neurologists’ decision to treat with immunotherapy as most treatments began prior to final results being available. However, we wish to add some points.

The authors have described a long latency period of around 17 days in getting the results of autoantibody testing in their center, after ordering the test. Surprisingly, even after residing in a developing country like India, we usually obtain the results of these autoantibody testing within two to three days. Thus the conclusion of authors might hold true for their own center, but its generalizability to various hospitals across the world is questionable. As more and more autoimmune encephalitis cases are being detected recently, testing for this disease is also becoming available more widely.

Secondly, the authors have not mentioned the exact working or provisional diagnosis of patients, in whom autoantibody testing was performed and they have only mentioned the presence of various symptoms like seizure, encephalopathy, etc. These symptoms are also found in diverse other etiologies including infectious and metabolic causes and they have also not mentioned the duration of symptoms before the autoantibody testing was ordered. There are clinical criteria to suspect autoimmune-mediated neurological diseases. ² It would have been better if the authors would provide how many of these patients had the primary working diagnosis of autoimmune-mediated neurological diseases and how many of them had only minor suspicion regarding the presence of central nervous system (CNS) autoimmunity. As the seropositivity percentage was only 10% in the study population and only a minor proportion of rest was treated with immunotherapy even with antibody negativity, it seems a considerable proportion did not satisfy the criteria for CNS autoimmune-mediated disease at the outset. In most of the previous series, antibody-positive autoimmune encephalitis constituted around half of the total cohort. Moreover, the authors have also not mentioned whether in all patients the serum and cerebrospinal fluid (CSF) sample for antibody testing was taken before starting immunotherapy, as it could have affected the yield of antibody testing.

Thirdly, the authors have not mentioned on what basis the treating physician decided to test the CNS-specific autoantibodies in serum, CSF, or both. Certain autoantibodies like anti-NMDA antibodies are more likely to be positive in CSF, whereas anti-GAD autoantibody is usually tested in serum. Similarly, the authors have also not mentioned how the treating physician decided to test for neuronal surface autoantibodies alone like anti-NMDA, VGKC, etc, or for autoantibodies against intraneuronal antigens alone like anti-Hu, anti-Ma, etc or both, as that also would have affected the result. Certain recently described autoantibodies like anti-IgLON and anti-DPPX were also most probably were not explored in this study, as well as the results of systemic autoantibody testing like anti-nuclear antibody and anti-TPO autoantibody.^3,4 Steroid-responsive encephalopathy with associated thyroiditis (SREAT) is also autoimmune encephalitis, with anti-TPO positivity, which responds favorably to steroids. ⁵

Lastly, case 3 was a 79-year-old female, who was finally diagnosed to have non-Alzheimer dementia and received supportive care only despite having anti-GAD65 positivity and thus should not be considered autoimmune encephalitis in an ideal sense. In previous studies also it has been mentioned anti-GAD65 positivity can occur as an epiphenomenon only. The authors should have taken caution while making their conclusion and the conclusion that autoantibody testing is not likely to help in clinical decision making might misguide physicians in the future in ordering these tests.