Immunological heterogeneity of multiple sclerosis in Sardinia and Sweden.
Subjects from Sardinia, Italy, are relatively homogeneous compared to Swedes. Although ethnically distant, both populations have similarly high multiple sclerosis (MS) incidence rates. Pro- and anti-inflammatory cytokines and their receptors, signalling molecules and other immune response-associated factors might influence MS pathogenesis, though definite proof is missing. The study of populations with similar MS incidence but different genetic and environmental background could make possible the definition of factors that relate to such background differences. We selected untreated female MS patients from Sassari, Sardinia, and Stockholm, Sweden, and corresponding sex- and age-matched healthy controls (HC), to study blood mononuclear cells (MNC) for mRNA expression of 20 immune response-related genes considered relevant in MS, employing real-time PCR. Higher expression of IL-12p40 mRNA was confined to MS from both Sassari and Stockholm, compared to corresponding HC. MS patients from Sassari, but not Stockholm, expressed higher TNF-alpha compared to corresponding HC. MS patients from Stockholm, but not Sassari, expressed higher IL-6. Indoleamine 2,3 dioxygenase (IDO), a molecule necessary in tolerance induction, was lower in MS from Stockholm compared to corresponding HC. This was not observed in Sassari. No differences were detected for other members of the IL-12 family, other Th1 and Th2 cytokines, and the signalling molecules Stat 4 and 6. The results corroborate a pro-inflammatory state in MS as reflected by high expression of IL-12, TNF-alpha and IL-6, although the extent of expression of TNF-alpha, IL-6 and IDO differs between strictly matched MS patients from different high-incidence areas. This might result from genetic and/or environmental differences. They may account for some of the discrepancies regarding immune response-related molecules previously reported in MS. In conclusion, a pro-inflammatory state exists in MS patients from Sassari as well as Stockholm. The changes of pro-inflammatory and other immune response-related variables differ however between the two MS populations. This may be attributed to the genetic and/or environmental background.
Huang
Yu-Min
YM
Neurotec Department, Karolinska Institute, Stockholm, Sweden. yu-min.huang@neurotec.ki.se
Liu
Xuan
X
Steffensen
Knut
K
Sanna
Alessandra
A
Arru
Giannina
G
Fois
Maria Laura
ML
Rosati
Giulio
G
Sotgiu
Stefano
S
Link
Hans
H
D000328:Adult; D016207:Cytokines / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D016753:Interleukin-10 / Q000235:genetics; D018664:Interleukin-12 / Q000235:genetics; D020382:Interleukin-18 / Q000235:genetics; D053727:Interleukin-18 Receptor alpha Subunit; D015847:Interleukin-4 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D007558:Italy; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology*; D018121:Receptors, Cytokine / Q000235:genetics*; D018123:Receptors, Interleukin / Q000235:genetics; D053701:Receptors, Interleukin-10; D053707:Receptors, Interleukin-12; D053724:Receptors, Interleukin-18; D019947:Receptors, Interleukin-6 / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D050797:STAT4 Transcription Factor; D050800:STAT6 Transcription Factor; D013548:Sweden; D015534:Trans-Activators / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D014366:Tryptophan Oxygenase / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016207:Cytokines; D004268:DNA-Binding Proteins; C508572:IL18R1 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D015850:Interleukin-6; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D053707:Receptors, Interleukin-12; D053724:Receptors, Interleukin-18; D019947:Receptors, Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D014366:Tryptophan Oxygenase