Anti-MMAB monoclonal antibody, clone 4C9

Methylmalonic acidemia (MMA), an inherited metabolic disease, results from genetic defects in methylmalonyl-CoA mutase or any of the proteins involved in adenosylcobalamin synthesis. This enzyme is classified into several complementation groups and genotypic classes. In this work we explain the biochemical, structural and genetic analysis of 25 MMA patients, from Iran. The diagnosis was established by the measurement of propionylcarnitine in blood using tandem mass spectrometry and confirmed using a gas chromatography-flame ionization detector. Using clinical, biochemical, structural and molecular analyses we identified 15 mut MMA, three cblA, one cblB, and four cblC-deficient patients. Among mutations identified in the MUT gene (MUT) only one, the c.1874A>C (p.D625A) variant, is likely a mut(-) mutation. The remaining mutations are probably mut(0). Here, we present the first molecular analysis of MMA in Iranian patients and have identified eight novel mutations. Four novel mutations (p.D625A, p.R326G, p.V157F, p.F379L) were seen exclusively in patients from northern Iran. One novel splice site mutation (c.2125-3C>G) in MUT and two novel mutation (p.N225M and p.A99P) in the MMAA gene were associated with patients from eastern Iran. The rs184829210 SNP was recognized only in patients with the novel c.958G>A (p.A320T) mutation. This study confirms pathogenesis of deficient enzyme activity in MUT, MMAA, MMAB, and MMACHC as previous observations. These results could act as a basis for the performance of pharmacological therapies for increasing the activity of proteins derived from these mutations.

Human spleen cells from an HIV-seropositive donor were immunized in vitro with the aa583-599 peptide conjugated to an heptalysyl core. This sequence was derived from the putatively HIV-immunosuppressive region of HIV1 gp41. The same conjugated peptide was used to immunize mice. One human and one mouse IgM monoclonal antibody (mAb) directed against the aa583-599 peptide were obtained. The two mAb had distinct patterns of reactivity against a panel of 42 peptides with modified sequences. Neither of the mAb inhibited the immunosuppressive effect of aa583-599 octopus-lys-conjugated peptide on anti-CD3 Ab-induced lymphoproliferation. In addition, both mAb did not neutralize cell-free virus transmission or enhance HIV infection. However, HmAb inhibited formation of syncytia between HIV 1 -infected (but not HIV2-infected cells) and non-infected target cells at concentrations above 20-mu-g/ml, whereas MmAb did not have any effect. The degree of conservation of the aa583-599 region makes HmAb a candidate for use as a group-specific reagent in future HIV1 passive immunotherapy protocols.