Autoantibodies against Central Nervous System Antigens and the Serum Levels of IL-32 in Patients with Schizophrenia

Abstract

<b><i>Background:</i></b> Schizophrenia is a disease of the nervous system, and immune system disorders can affect its pathogenesis. Activation of microglia, proinflammatory cytokines, disruption of the blood-brain barrier due to inflammation, activation of autoreactive B cells, and consequently the production of autoantibodies against system antigens are among the immune processes involved in neurological diseases. Interleukin-32 (IL-32) is a proinflammatory cytokine that is essential in activating innate and adaptive immune responses. This study aimed to measure the serum level of IL-32 as well as the frequency of autoantibody positivity against several nervous system antigens in patients with schizophrenia. <b><i>Material and Methods:</i></b> This study was conducted on 40 patients with schizophrenia and 40 healthy individuals in the control group. Serum IL-32 levels were measured by ELISA. The frequency of autoantibodies against Hu, Ri, Yo, Tr, CV2, amphiphysin, SOX1, Zic4, ITPR1, CARP, glutamic acid decarboxylase GAD, recoverin, titin, and ganglioside antigens was measured by the indirect immunofluorescence method. <b><i>Results:</i></b> Serum IL-32 levels in patients with schizophrenia were significantly higher compared to the control group. The frequency of autoantibodies against GAD and RI antigens in patients with schizophrenia was significantly higher than in the control group. Autoantibodies were positive in 8 patients for GAD antigen and 5 patients for RI antigen. Autoantibodies were also positive in 2 patients for CV2, 1 patient for Hu, and 1 patient for CARP. Negative results were reported for other antigens. <b><i>Conclusion:</i></b> Our findings suggest that elevated the serum IL-32 level and autoantibodies against GAD and RI antigens may be a reflection of immune system dysregulation in patients with schizophrenia.

Antineuronal autoantibodies induced paraneoplasic syndrome in schizophrenia spectrum disorders: case report

“…Park et al 15 reported that anti-Ma2 antibody encephalitis could cause psychiatric symptoms like aggressiveness, memory impairment, decreased speech, anxiety, disorganized language, and depressed mood. In a recent study, the prevalence of anti-GAD and anti-Ri antibodies in schizophrenia patients was higher than in controlled patients 16 . Keshavarz et al 16 showed that among 40 patients treated for schizophrenia, eight were positive for anti-GAD antibody, five for anti-Ri antibody, two for anti-CV2 antibody, one for anti-Hu antibody, and one for anti-CARP antibody.…”

“…In a recent study, the prevalence of anti-GAD and anti-Ri antibodies in schizophrenia patients was higher than in controlled patients 16 . Keshavarz et al 16 showed that among 40 patients treated for schizophrenia, eight were positive for anti-GAD antibody, five for anti-Ri antibody, two for anti-CV2 antibody, one for anti-Hu antibody, and one for anti-CARP antibody. Several literature publications have suggested a relationship between schizophrenia and antineuronal antibodies in the context of PNS 10 , 15 , 16 .…”

“…Keshavarz et al 16 showed that among 40 patients treated for schizophrenia, eight were positive for anti-GAD antibody, five for anti-Ri antibody, two for anti-CV2 antibody, one for anti-Hu antibody, and one for anti-CARP antibody. Several literature publications have suggested a relationship between schizophrenia and antineuronal antibodies in the context of PNS 10 , 15 , 16 . Treating the tumor can solve psychiatric symptoms better than psychotic treatment 8 .…”

DNA methylation changes in association with trauma-focused psychotherapy efficacy in treatment-resistant depression patients: a prospective longitudinal study

“…Looking at regional analysis, we have identified several significant DMRs annotated in genes related to inflammatory and immune processes, such as LTA , GFI1 , ARID5B , CD52 , TNFSF13 , SLFN13 , LST1 , TNFRSF1A , CCRL2 , and IL32 . Moreover, some significant genes are known to be related to schizophrenia risk, such as LTA (Arab & Elhawary, 2015 ; Pandey et al, 2018 ), ARID5B (Drago et al, 2014 ), TNFSF13 (Catts & Weickert, 2012 ), TNFRSF1A (Gandal et al, 2018 ), IL32 (Keshavarz et al, 2022 ), LDLRAD4 (Kikuchi et al, 2003 ), and GAS7 (Z. Zhang et al, 2016 ), attention-deficit hyperactivity disorder, like GFI1 (Miyake et al, 2021 ), bipolar disorder, including TNFRSF1A (Gandal et al, 2018 ), and autism spectrum disorder, like TNFRSF1A (Gandal et al, 2018 ) and C11orf21 (Dall’Aglio et al, 2018 ). Notably, another significant gene is LST1 (Leukocyte Specific Transcript 1), which plays a role in immune system regulation.…”

Neuronal autoantibodies in the cerebrospinal fluid of 148 patients with schizophrenia and 151 healthy controls

“…Schizophrenia is a progressive and chronic psychiatric disorder affecting approximately 0.3 % of people worldwide [ 1 , 2 ]. In recent years, schizophrenia has been considered a heterogeneous condition with differential etiological factors [ 3 ], such as neuroinflammation [ 4 ], genetic abnormalities [ 5 ], and autoimmune disorders [ 6 , 7 ].…”