Do patients with schizophreniform and bipolar disorders show an intrathecal, polyspecific, antiviral immune response? A pilot study

Abstract

BackgroundWe previously described inflammatory cerebrospinal fluid (CSF) alterations in a subgroup of patients with schizophreniform disorders and the synthesis of polyspecific intrathecal antibodies against different neurotropic infectious pathogens in some patients with bipolar disorders. Consequently, we have measured the prevalence of a positive MRZ reaction (MRZR)—a marker for a polyspecific, antiviral, intrathecal, humoral immune response composed of three antibody indices for the neurotropic viruses of measles (M), rubella (R), and varicella zoster (Z)—in these patients.MethodsWe analyzed paired CSF and serum samples of 39 schizophreniform and 39 bipolar patients. For comparison, we used a group of 48 patients with other inflammatory neurological disorders (OIND) and a cohort of 203 multiple sclerosis (MS) patients.ResultsWe found a positive MRZR in two patients with schizophreniform disorders (5.1%); both suffered from schizodepressive disorders without any other signs suggestive of MS. None of the bipolar patients (0%) and four members of the OIND group (8.3%) showed a positive MRZR. In the MS cohort, a positive MRZR was found significantly more frequently [in 99 patients (48.8%)] than in the other patient groups (p > 0.001). In summary, we did not find a positive MRZR in a relevant subgroup of patients with schizophreniform or bipolar disorders.ConclusionsOur results indicate that the MRZR is highly specific to MS. Nevertheless, two schizodepressive patients also had a positive MRZR. This finding corresponds to the few MRZR-positive patients with OIND or other autoimmune disorders with central nervous involvement, implicating that the MRZR specificity for MS is high, but not 100%.

Antibody indices of infectious pathogens from serum and cerebrospinal fluid in patients with schizophrenia spectrum disorders

“…This phenomenon seems to be rare (at 2% in our cohort, 3% in the subgroup of chronic SSD). In line with this, an earlier study described a positive MRZ reaction in two of the 39 (5%) patients with SSDs [14]. Nevertheless, a similar rate of multiple positive AIs was found in our control group of IIH patients.…”

Anti-Cyclic Citrullinated Peptide Antibody Index in the Cerebrospinal Fluid for the Diagnosis and Monitoring of Rheumatoid Meningitis

“…Indeed (since the amount of anti-CCP antibodies in CSF may be due to a passive diffusion from serum, blood–CSF barrier dysfunction, and eventual intrathecal synthesis), by the use of this index it is possible to identify if a fraction of the CSF anti-CCP antibodies is produced within the central nervous system, indicating local inflammation. This approach has been used for a long time in the study of viral infections or to detect polispecific immune responses in multiple sclerosis [ 24 , 27 , 28 ]. Notably, the normal anti-CCP antibody index that we found in a woman affected by RA with elevated serum anti-CCP antibodies but without RM, further suggests that anti-CCP intrathecal synthesis is pathognomonic of RM and would be detectable only in patients with the active disease.…”

“…Theoretically, in the absence of intrathecal synthesis, the AI values calculated by the described formulas should be 1; however, due to several factors (such as inter-individual variability and specific test coefficient variation), AI values lower than 1.5 are considered physiological [ 24 ]. These well-known formulas are currently used to evaluate intrathecal synthesis in viral and autoimmune diseases and to detect polispecific immune response to the three neurotropic viruses (measles (M), rubella (R), and varicella zoster (Z)) in multiple sclerosis patients (the so-called “MRZ reaction”) [ 24 , 27 , 28 ].…”

Diagnosing Organic Causes of Schizophrenia Spectrum Disorders: Findings from a One-Year Cohort of the Freiburg Diagnostic Protocol in Psychosis (FDPP)

“…The screening suggested here was based on our own clinical experiences and was adapted over the last few years. For example, the MRZ reaction was also recorded temporarily, but this did not have relevant clinical consequences and was not further investigated in the course of the screening [60]. Further blood markers (e.g., ceruloplasmin, broader pathogen search, genetic testing) or additional investigations (e.g., FDG-PET) could be useful in some patients (see Table 1).…”