L.J. Barkai1, E. Sipter1, D. Csuka1, Z.Prohaszka1, N.Hosszufalusi1
1Semmelweis University, IIIrd Department of Internal Medicine, Budapest, Hungary.
Plasma concentration of lectin complement pathway member MASP3 among T2DM patients during and after bacterial infection
Background: 
Bacterial infections among type 2 diabetes (T2DM) are more frequent and severe, mortality rates are higher in comparison with non-diabetic patients. The background of this phenomenon is not fully understood, HbA1c and infection risk is not evidently associated. The complement system plays an important role in response to pathogens. One of its three activation pathways is the lectin pathway, where members can bind to carbohydrate molecules on the surface of pathogens resulting in the activation of MBL- associated serine proteases (MASPs). MASP2 with other members of the lectin pathway can form activatory complexes, while MASP3 seems to have an inhibitory role on complement activation. 
Aim: 
We hypothesize that glycated proteins in T2DM may serve as false recognition patterns which can lead to altered complement activation. The goal of our study was to describe a possible role of MASP2 and MASP3 on increased risk of bacterial infections among T2DM patients. 
Method: 
Prospective study including patients with clinical diagnosis of acute community acquired bacterial infections with or without T2DM, according to WHO criteria. Patients with immunological, hematological, oncological illnesses were excluded. Plasma concentrations of MASP2 and MASP3 were measured using commercial ELISA kits. After a minimum of three-month infection-free period complement and clinical laboratory parameters were reassessed. Statistical analysis was performed using GraphPad Prism 5. 
Results: 
171 with T2DM and 140 non-diabetic (ND) subjects were involved, 81 of the T2DM (47.4%) and 69 of the ND (49.3%) were men. 109 T2DM and 84 ND subjects were rechecked in an infection-free period. Median age (25th-75th percentile) did not differ between the two groups: T2DM: 72 (64.5-80) years, ND: 71 (59-81) years. HbA1c levels in the T2DM group were higher than in the ND group (7.45 [6.4-8.63] vs. 5.4 [5.1-5.8] %), p<0.0001. Concentrations of MASP2 were higher, MASP3 were lower during infection compared to the infection-free period, in both groups (p<0.0001, for both parameters in both groups). Higher levels of MASP3 were found among T2DM patients compared to non-diabetic subjects in presence (p<0.0001) and in absence (p=0.01) of the infection. 

Discussion: 
MASP2 concentrations increased while MASP3 decreased during infection compared to an infection-free period in both T2DM and ND patients. This is in coherence with the literature as the two seem to have different regulation on the lectin complement pathway. However, MASP3 concentrations were significantly higher in the T2DM group compared to ND subjects in presence and in absence of the infection. This may lead to an altered activation of the lectin complement pathway.