A Preliminary Investigation On The Role Of The Antibody Against Lysosome-associated Membrane Protein-2 In MPO-ANCA Associated Vasculitis

Background Antineutrophil cytoplasmic autoantibodies(ANCA)associated vasculitis(AAV) is divided into granulomatosis polyangiitis(GPA), microscopic polyangiitis(MPA) and eosinophilic granulomatosis polyangiitis(EGPA). ANCA against myeloperoxidase(MPO-ANCA) associated vasculitis(MPO-AAV)isthe predominant type of AAV in China.MPO-ANCA is considered to have pathogenic role in MPO-AAV currently, but its exact pathogenesis is not yet clear.It was first reported by Kain that anti-lysosome-associated membrane protein-2 antibody(Anti-LAMP-2)could be detected in 80% patients with Pacuci-immune necrotizing and crescentic glomerulonephritis(NCGN) diagnosed pathologically. Based on the positive association between Anti-LAMP-2 and the NCGN activity and also, the successful animal model with AAV kidney damage induced by this autoantibody. Kain thought Anti-LAMP-2 might be a newtype of pathogenic antibody for AAV.However, a study from Roth reported that only 21% of the patients with AAV had Anti-LAMP-2 and no Anti-LAMP-2 could be found in rat glomerular.And there was no glomerular nephritis in rats which were injected with Anti-LAMP-2. Therefore, the pathogenic role of Anti-LAMP-2 in AAV is still controversial currently. Up to now, there is no report about the research on Anti-LAMP-2 in MPO-AAVin china.Objective To preliminarily investigate the prevalence and significance of Anti-LAMP-2in MPO-AAV in china.Methods 128 patients(patient group)with MPO-AAV diagnosed for the first time and without any therapy and 30 healthy people(control group) were recruited in this prospective study. Clinical documents of all patients were collected and the degree of their disease activities was evaluated by Birmingham Vasculitis Activity Score(BVAS).The peripheral blood from all patients was taken to detect the Anti-LAMP-2,Myeloperoxidase-antineutrophil cytoplasmic antibody(MPO-ANCA),lysosome-associated membrane protein-2(LAMP-2), Myeloperoxidase(MPO), activated complement C5 a and Ceruloplasmin(Cp) by enzyme linked immunosorbent assay(ELISA).These data and the clinical manifestations were comparatively analyzed between Anti-LAMP-2 positive and negative group, and the relationships among them were also investigated.Results1.The difference of the gender(male: female, 51:77vs 12:18, χ2=0.00, P=0.987)and age(63.27±15.14vs60.73±8.76 yearsold,t=1.218,P=0.227)between the case group and the control group was not statistically significant.The common clinical damage in patients group were kidney, lung, joint, heart, gastrointestinal, peripheral nerve, mouth,skin, central nervou, muscle, eye, ear, nose, liver, throat. The most common organ damage is nephric damage(90 / 128, 70.31%) and pulmonary damage(86/128,67.19%).2.Both the level of Anti-LAMP-2 and LAMP-2 in patient group were higher than that in control group [absorbance value: 0.276(0.047,1.813)vs0.185(0.127,0.304)for Anti-LAMP-2,z=-3.983, P<0.001;0.142(0.051,1.064)vs 0.082(0.049,0.281)for LAMP-2, z=-5.112,P<0.001].3.The prevalence of Anti-LAMP-2 was 48.44% in MPO-AAV patients while in patients with nephric damage, this prevalence was 48.89%(44/90). This prevalenc also showed no significant difference between the patients with and without nephric lesion(48.89% vs47.37%,χ2=0.025,P>0.05),with and without pulmonary damage(50.00% vs45.24%,χ2=0.256,P>0.05).The level of Anti-LAMP-2 showed no significant difference betweenthe patients with and without nephric damage[0.269(0.047,1.790)vs 0.280( 0.032, 1.821),z=-0.073, P>0.05 ],with and without pulmonary damage[0.286(0.050,1.820) vs 0.258(0.033,1.913),z =-0.312, P>0.05].This no-significant difference of Anti-LAMP-2 level was also found between the patients with and without the damage of joint, heart, gastrointestinal tract, peripheral nervous, oral cavity and skin(P>0.05 in all comparison).4.The levels of C5 a, MPO,LAMP-2 and Cp in patients with Anti-LAMP-2 were significantly higher than that in patients without Anti-LAMP-2(565.66±504.72 vs369.98±134.05 ng/ml,t=-2.764,P<0.01;908.49±686.52 vs 460.89±208.14 IU/L,t=-3.506,P<0.001;0.328±0.298 vs 0.128±0.060,t=-5.181,P<0.001;655.83±326.13 vs 452.28 ± 79.27 ng/ml, t=-3.247, P<0.01, respectively). There was no statistically significant difference between the two groups when comparing their gender composition, age, course of disease, the disease activity(BVAS), MPO-ANCA,ESR, CRP, C3, 24 hours urinary protein quantitation, occult blood in urine and serium creatinine levels.5.In the group of patients with Anti-LAMP-2, the level of Anti-LAMP-2 had markedly positive correlations with either of C5 a, MPO,LAMP-2 and Cp(rs=0.056, P<0.001;rs=0.525, P<0.001; rs=0.723, P<0.001;rs=0.714,P<0.001,respectively) while there was no obvious relationship between Anti-LAMP-2 and age, course of disease, BVAS,major organ damage, ESR, serium CRP, C3, serium urea nitrogen, creatinine, uric acid,urine occult blood, 24 hour urinary protein quantitation, respectively(P > 0.05).Conclusion1. MPO-AAV is common in AAV patients in our country, The most common damaged organ is is kidney and lung.2. Anti-LAMP-2 was a common autoantibody in MPO-AAV in our country, its prevalence was 48.44%.3. Anti-LAMP-2 may be independent from autoantibody MPO-ANCA. It might play an important role in the pathogenesis of clinical damage in MPO-AAV by someway like promoting the activation of alternative complement pathway and combining with its elevated autoantigen LAMP-2.4. The MPO-ANCA is likely to contribute to Anti-LAMP-2 production by improving LAMP-2 antigen level in blood circulation resulting from the degranulation and/or inflammatory distruction of neutrophils, which might be one of the machnisms for the production of Anti-LAMP-2.5. The exact role and significance of Anti-LAMP-2 in the pathogenesis of MPO-AAV remains to be further explored.