New protocols for treatment of class IV lupus nephritis with emphasis on rituximab as the sole maintenance therapy

Objective: A safe and effective treatment for lupus nephritis [LN]

Design: An 8-year prospective study

Setting: Hospital-based

Subjects: Three groups of patients with class IV LN; comparison of 2 new treatment-protocols for class IV LN with a retrospective group of patients who had received the standard treatment for LN

Intervention: The 2 treatment groups had received an induction phase of monthly intravenous Cyclophosphamide, Mycophenolate [MP] and Prednisone [P]. The maintenance phase in the first group was only MP and P, while patients in the second group had received only yearly Rituximab infusions

Main outcome measures: Morbidity and mortality

Results: Patients in the first group did not have significant relapses, yet had 10 episodes of infections during the maintenance phase. In the second group, there were five treatment failures, yet none had renal deterioration, infections or death. In the third group, seven relapses occurred during the induction period and three in the maintenance one. Moreover, complications included 1 death of disseminated sepsis, 12 cases of chronic renal failure, three kidney losses, 16 episodes of major infections, two cases of aseptic necrosis, two cases of gonadal failure, two cases of hemorrhagic cystitis and 2 cases of retinal deposits

Conclusions: Rituximab infusions, used once yearly, are effective and a safe maintenance therapy for most patients with LN after a short course of three anti-proliferative agents. In those who failed to respond, MP and P are more effective and safer than the standard protocol

Whole blood assays to identify Th1 cell antigens and peptides encoded by mycobacterium tuberculosis-specific RD1 genes

To identify Th1 cell-stimulating antigens/peptides encoded by the genes predicted in the Mycobacterium tuberculosis-specific genomic region of difference [RD]1, deleted in Mycobacterium bovis Bacille Calmette-Guerin[BCG], by using synthetic peptides and whole blood from tuberculosis [TB] patients. Heparinized peripheral blood was obtained from culture-proven pulmonary TB patients [n = 16] attending the Chest Disease Hospital, Kuwait. Whole blood was diluted with tissue culture medium RPMI-1640 and tested for Th1 cell stimulation using antigen-induced proliferation and interferon- [IFN-] secretion assays. The antigens included a peptide pool of 220 peptides covering the sequence of 12 open reading frames [ORFs] of RD1 [RD1mix], peptide pools of RD1 ORF5 [ORF5mix], ORF6 [ORF6mix] and ORF7 [ORF7mix], and individual peptides of ORF6 [P6.1-P6.6] and ORF7 [P7.1-P7.6]. M. tuberculosis culture filtrate, cell walls and whole-cell M. bovis BCG were used as complex mycobacterial antigens. The results obtained with different antigens and peptides were statistically analyzed for significant differences using Z test. The complex mycobacterial antigens [culture filtrate, cell walls and M.bovis BCG] and RD1mix induced comparable [p > 0.05] positive antigen-induced proliferation and IFN- responses with whole blood from TB patients. However, the positive IFN- responses induced by ORF6mix and ORF7mix were higher than ORF5mix. Among the individual peptides, P6.4 and P7.1 of ORF6 and ORF7, respectively, induced the highest IFN- responses, suggesting that these peptides represented the immunodominant Th1 cell epitopes of RD1 ORF6 and ORF7 in the patients tested. The whole blood assays with synthetic peptides are useful to identify Th1 cell antigens/peptides encoded by genes located in M. tuberculosis-specific genomic regions

Cell-mediated immune responses to complex and single mycobacterial antigens in tuberculosis patients with diabetes

To evaluate cell-mediated immune [CMI] response in diabetic and non-diabetic tuberculosis [TB] patients and healthy subjects in response to complex, fractionated and single antigens of Mycobacterium tuberculosis. Peripheral blood mononuclear cells [PBMC] were obtained from patients suffering from pulmonary TB and type II diabetes [n = 7], pulmonary TB without diabetes [n = 10] and healthy subjects without TB and diabetes [n = 10]. PBMC were assessed for CMI responses in antigen-induced proliferation assays in response to complex mycobacterial antigens [whole cells, cell walls and culture filtrate of M. tuberculosis], a battery of naturally purified or recombinant produced secreted [ESAT6, MPT59, MPT64 and MTB38] and cytosolic [MTB10, MTB70, ML10, ML28, ML36, ML65 and MB65] mycobacterial antigens and fractionated culture filtrate proteins [fractions F1-F10] of M. tuberculosis. The majority [>70%] of diabetic and non-diabetic TB patients and healthy subjects responded to the complex antigens of M. tuberculosis. However, among the single antigens, ESAT6 was most frequently recognized by TB patients with and without diabetes, but least recognized by healthy subjects. The secreted antigens MPT59 and MPT64 were recognized by all the groups, whereas the cytosolic antigens were recognized best by healthy subjects. When tested with fractionated secreted proteins present in the culture filtrate of M. tuberculosis, the best responses in both diabetic and non-diabetic TB patients were obtained with fractions containing low-molecular-weight proteins. Diabetic and non-diabetic TB patients respond frequently to secreted low-molecular-weight ESAT6 antigen of M. tuberculosis, indicating that this antigen may be useful in the diagnosis of TB in both the groups