A substantial number of Rasmussen syndrome patients have increased IgG, CD4+ T cells, TNFalpha, and Granzyme B in CSF.
OBJECTIVE
We studied the immunologic molecules in cerebrospinal fluid (CSF) and discussed their evolutional changes in pediatric patients with Rasmussen syndrome (RS).


METHODS
CSF samples collected from 27 patients with RS (average onset age, 7.5 +/- 5.6 years) were studied. Cell count, protein, glucose, albumin, chloride, and immunoglobulin G (IgG) levels were measured by conventional methods. Surface markers of lymphocytes in CSF were examined by a cell sorter. Granzyme B, interferon gamma (IFNgamma), interleukin 4 (IL-4), tumor necrosis factor alpha (TNFalpha), and IL-12 in CSF were quantitated by enzyme-linked immunosorbent assay (ELISA). Autoantibodies against GluR epsilon2 (NR2B) were examined by immunoblot.


RESULTS
The data of the first CSF examination showed that IgG levels (Mann-Whitney U test, p < 0.01), CD4(+) T cells (p = 0.02), TNFalpha levels (p < 0.01), and Granzyme B levels (p < 0.01) were elevated compared with disease controls. White blood cell count, IFNgamma level, IL-12 level, and Granzyme B level were elevated, especially in the early stage of disease. CD4(+) T cells, CD8(+) cells, CD3(+) T cells, IgG levels, and TNFalpha levels were elevated at all stages of disease evolution. Protein levels and albumin levels were elevated in the progressed stage. Autoantibodies against GluR epsilon2 (NR2B) (IgG) were found in 50% of patients in the early stage, and the positive rate was low at the progressed stage.


CONCLUSIONS
The present findings suggest that complex pathophysiologic mechanisms involving CD4(+) T cells and CD8(+) T cells change evolutionally during the progression of RS. A crucial cytotoxic process occurs in the early stage, and declines in the progressed stage.
Takahashi
Yukitoshi
Y
National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan. takahashi-ped@umin.ac.jp
Mine
Jyun
J
Kubota
Yuko
Y
Yamazaki
Etsuko
E
Fujiwara
Tateki
T
D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002452:Cell Count / Q000379:methods; D002648:Child; D002675:Child, Preschool; D004660:Encephalitis / Q000134:cerebrospinal fluid* / Q000150:complications / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D053804:Granzymes / Q000134:cerebrospinal fluid*; D006801:Humans; D007074:Immunoglobulin G / Q000134:cerebrospinal fluid*; D007223:Infant; D007376:Interleukin-2 / Q000134:cerebrospinal fluid; D008297:Male; D011506:Proteins / Q000378:metabolism; D018709:Statistics, Nonparametric; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid*; D055815:Young Adult
D007074:Immunoglobulin G; D007376:Interleukin-2; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D053804:Granzymes