Association of immune mediators at diagnosis of Type 1 diabetes with later clinical remission.
OBJECTIVE
We tested the hypothesis that systemic concentrations of cytokines, chemokines or soluble cytokine receptors predict or accompany clinical remission in Type 1 diabetes (T1D).


METHODS
In a prospective, multicentre study, 48 patients with newly diagnosed T1D and 55 age-matched healthy control subjects were investigated. Blood was drawn 3-7 days after the diagnosis and then 3-4 months later. Patients were grouped into partial remitters or non-remitters by the degree of clinical improvement defined by HbA(1c) (threshold 7.5%) and daily insulin dose (threshold 0.38 IU/kg/day). Systemic concentrations of 17 immune mediators were analysed in serum or plasma. In addition, autoantibodies against insulin (IAA), IA-2 (IA-2A) and GAD65 (GADA) were quantified.


RESULTS
All 17 immune mediators showed remarkable intra-individual stability in their systemic concentrations over time. As a consequence, partial remission was not accompanied by changes in mediator levels except for a moderate decrease of interleukin (IL)-1ra concentrations (P = 0.02) and IL-10 concentrations (P = 0.01) in non-remitters. Baseline levels were associated with the later clinical course in that low levels of interferon gamma (P = 0.01), IL-10 (P = 0.03) and IL-1R1 (P = 0.009) concentrations were observed in partial remitters.


CONCLUSIONS
We conclude that the systemic immunoregulatory state at diagnosis of T1D is predictive of clinical improvement during the remission phase. There was no general change in systemic immune reactivity in the months after diagnosis and initiation of insulin therapy.
Schloot
N C
NC
German Diabetes Centre, Heinrich Heine University, Düsseldorf, Germany. schloot@ddz.uni-duesseldorf.de
Hanifi-Moghaddam
P
P
Aabenhus-Andersen
N
N
Alizadeh
B Z
BZ
Saha
M T
MT
Knip
M
M
Devendra
D
D
Wilkin
T
T
Bonifacio
E
E
Roep
B O
BO
Kolb
H
H
Mandrup-Poulsen
T
T
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D018925:Chemokines / Q000032:analysis / Q000097:blood*; D016207:Cytokines / Q000032:analysis / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis*; D005260:Female; D006801:Humans; D008297:Male; D011446:Prospective Studies; D018121:Receptors, Cytokine / Q000032:analysis / Q000097:blood*; D012074:Remission Induction
D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines; D018121:Receptors, Cytokine