annular erythema developing for 10 years. Bull Soc Fr Dermatol Syphiligr Dec, 1962; 69: 840 -842. 3 Branfor WA, Farr PM, Porter DI. Annular vasculitis of the head and neck in a patient with sarcoidosis. Br J Dermatol, 1982; 106: 713-716. 4 Nousari HC, Kimyai-Asadi A, Stone JH. Annular leukocytoclastic vasculitis associated with monoclonal gammopathy of unknown significance. J Am Acad Dermatol, 2000; 43: 955-957. 5 Aram H, Rubinstein N, Granot E. Annular erythema with histologic features of leukocytoclastic vasculitis in ulcerative colitis. Cutis., 1985; 35: 250 -252. 6 Kelly RI, Cook MG, Marsden RA. Annular vasculitis associated with pregnancy. Br J Dermatol, 1993; 129: 599-601. 7 Chiu CS, Chang YC, Chung WH et al. Annular leucocytoclastic vasculitis induced by chlorzoxazone. Br J Dermatol, 2004; 150: 153. 8 Ruiz Villaverde R, Blasco Melguizo J, Martin Sanchez MC.Naranjo sintes annular leucocytoclastic vasculitis: response to dapsone.

2530 Macrophage migration inhibitory factor (MIF) is a key mediator of the innate immune system by promoting pro-inflammatory functions, being involved in the pathogenesis of the sepsis, in inflammatory and autoimmune diseases, growth and cell differentiation, and in carcinogenesis. The recessive CC gene variant in -173G/C in the promoter region causes higher levels of MIF and it has been associated with sepsis, gastric cancer, and autoimmune diseases. We aimed to see whether this genetic variant influenced the clinical outcome of acute myeloid leukemia (AML) patients. Population study consisted of 277 AML patients from the Spanish cooperative CETLAM group. Median age of the patients was 45 (range, 15–74). According to MRC classification, 11% were of good risk, 70% of intermediate risk, and 11% of poor risk. For 8% of the patients MRC cytogenetical data was not available. Multivariate analysis for outcome was performed including age, MRC classification and leukocyte count. Results showed that recessive CC gene variant was associated with worse outcome than the other two genotypes (GG+GC). Thus, this gene variant was associated with lower overall survival (OS): 0% vs 28%, p<0.001, OR=5.19, p=0.002; and disease free survival (DFS): 0% vs 31%, p=0.003, OR=7.35, p=0.007 (Figure 1). Considering only patients with intermediate MRC, this recessive CC gene variant also retained its impact for OS (0% vs 27%, p=0.001; OR=5.96, p=0.003) and for DFS (0% vs 31%, p=0.005, OR=6.82, p=0.01). We restricted the analysis to patients who underwent allo-SCT, and this variant retained the worst prognostic value for OS (0% vs 54%, p=0.014, OR=10.89, p=0.037) and for DFS (0% vs 41%, p=0.027, OR=9.09, p= 0.05). Because this variant is associated with high expression of MIF, we analyzed MIF mRNA expression in healthy donors, in low and high risk myelodisplastic syndrome (MDS) patients, and in AML patients. Results showed a progressive increase of MIF expression from healthy donors to AML, presenting AML patients 31 fold higher MIF expression than donors (p<0.001). Furthermore, we analyzed the clinical impact of this recessive CC variant in MIF gene in a Spanish multicentre study of 490 adult donor-patient pairs who underwent HLA identical sibling allo-SCT. All patients were diagnosed with hematological malignancies. Median age was 45 (range, 16–69), 33% were in advanced phase of disease, and 38% received a reduced intensity conditioning regimen. This recessive CC gene variant when present in the patient was associated with higher frequency of death by sepsis or infection (83% of patients with this variant died of sepsis vs 17%, p=0.005). When the analysis was restricted to acute leukemia and MDS patients (N=234), this recessive CC gene variant was associated with higher transplant related mortality (73% vs 29%, p=0.02). Finally, we analyzed IFNγ production in peripheral blood of 180 blood donors after stimulation with cytomegalovirus (CMV) and phytohemagluttinin (PHA). Results showed that this variant (CC) was associated with higher IFNγ production after CMV exposure (p=0.003) and higher IFNγ production after PHA exposure (p=0.007). In conclusion, these results indicate the adverse prognostic impact of recessive CC gene variant in AML patients.Figure 1:A: Probability of overall survival (OS) and B: Probability of disease free survival (DFS) in the all group of AML patients according to 173G/C gene variant in MIF. GG+GC: patients carrying homozygous dominant variant + patients carrying heterozygous gene variant. CC: patients carrying recessive gene variant. Values obtained at multivariate analysis (OR and p) are shown.Figure 1:. A: Probability of overall survival (OS) and B: Probability of disease free survival (DFS) in the all group of AML patients according to 173G/C gene variant in MIF. GG+GC: patients carrying homozygous dominant variant + patients carrying heterozygous gene variant. CC: patients carrying recessive gene variant. Values obtained at multivariate analysis (OR and p) are shown. Disclosures: No relevant conflicts of interest to declare.

3052 Innate immunity, by initiating an inflammatory response and by activating the adaptive immunity, is crucial in the onset of aGvHD after allo-SCT. DEBF1 belongs to the defensins family, which are antimicrobial peptides produced by leukocytes and a variety of mucosa and epithelial cells. They act as key effectors of innate immunity and regulate adaptive immunity; in the intestinal tract, they present antimicrobial activity, and low levels appear in intestinal chronic inflammation. DEBF1 has in the promoter region three gene variants (-52G/A, -44G/C, -20G/A) which are associated with infectious diseases and with chronic inflammation, however incongruent results have been obtained by different groups. We aimed to see whether there is an impact of gene variants of DEBF1 on aGVHD and in the inflammatory response in healthy blood donors. Population study consisted of 490 adults donor-patients pairs who underwent HLA identical sibling allo-SCT. All patients were diagnosed with hematological malignancies. Median age was 45 (range, 16–69), 33% were in advanced phase of disease, and 38% received a reduced intensity conditioning regimen. Association results showed that recessive -52A gene variant in DEBF1 when present in the donor was associated with higher aGvHD grades III-IV (24% vs 11%, p=0.023). At multivariate analysis, this gene variant retained the highest significance (OR=2.11, p=0.02). We performed functional studies in 180 blood donors for this gene variant to find out if it influenced the global production of IL12, IL13, IL15, IL17, and of Th1/Th2 cytokines after phytohemagglutinin (PHA) and cytomegalovirus (CMV) exposure. Further, we determined the percentage of IFN γ producing NK cells, NKT cells, CD8+ cells and CD4+ by cells after CMV exposure in 120 blood donors according to this gene variant. After PHA exposure, donors carrying this variant had lower production of IL13 (81 pg/mL vs 135 pg/mL, p=0.05), IL2 (1072 pg/mL vs 1527 pg/mL, p=0.006), IL4 (31 pg/mL vs 67 pg/mL, p=0.004) and IFN γ (31 pg/mL vs 67 pg/mL, p=0.02) (Figure 1), indicating a lower anti-inflammatory response. These cytokines play an important role in the aGvHD development, as IL13 is known by its anti-inflammatory properties, IL2 enhances T reg proliferation reducing aGvHD, IL4 is involved in the reduction of GvHD by NKT cells and IFN γ can present immunosuppressive activity inhibiting GvHD. This lower anti-inflammatory response could explain the higher incidence of severe aGvHD for this recessive -52A gene variant. Curiously, the recessive gene variant, when it was present in the donor, was associated with a lower incidence of cause of death by infection or sepsis in the same cohort of patients submitted to allo-SCT (12.5% of individuals carrying this variant died by infection or sepsis vs 87.5% of death by other causes in individuals with this variant, p=0.04). Functional studies showed that after CMV exposure, this variant presented much higher percentage of IFN γ producing NK cells (p=0.005) and IFN γ producing NKT cells (p=0.03); when the analysis was restricted to IgG positive donors for CMV, this association was stronger (p=0.0002 and p=0.006, for % of IFN γ producing NK cells and NKT cells, respectively) (Figure 2), indicating a different role for this variant after CMV infection. These results indicate an important impact of the -52A recessive gene variant in DEBF1 in the clinical outcome after allo-SCT in terms of GvHD and infection, which might be due to modifications in the anti-inflammatory response pattern. Disclosures: No relevant conflicts of interest to declare.