Wednesday, September 15, 2010

IN THE NEWS- Basophils add fuel to LUPUS fire!

SLE and lupus nephritis has been a tough disease entity both for patients and physicians. Lot of different cells have been implicated in the pathogenesis and many drugs have come, conquered the market for a while and then gone! Besides steroids, none of the other medications have truly beat lupus. Cytoxan, Rituxan and Cellcept being the major players, all work well but disease can recur.
Recently, a nice basic science paper in Nature Medicine found some possible role of basophils in the pathogenesis of lupus. Using mice models, they showed that activation of basophils by autoreactive IgE causes the homing of lymph nodes promoting more TH2 cell differentiation and enhancing self reactive antibodies and leading to lupus like nephritis. Apparently humans with SLE have elevated serum IgE, self reactive IgE and activated basophils and can cause this second hit and worsening lupus nephritis.

In these experiments, B cell regulator was deficient and that led to spontaneous development of Anti DSDNA and lupus like nephritis and elevated IL-4 and IgE suggesting a role of Basophils, as they use the  TH2 dependent pathway.  So the postulated pathway is LUPUS disease has activated Ig E immune complexes and autoantigens and that activates basophils which upregulates MHC Class II and CD62L and IL-4 initiation that will eventually activate B cells and autoantibody formation leading to lupus nephritis!

A nice editorial in NEJM following this points out few important limitations. If the above was the case of pathogenesis of lupus nephritis, then almost all SLE patients should have IgE activation but only 30% of patients have detected auto antibodies to IgE.  This talks only about a TH2 mediated pathogenesis but Th17 has also been implicated in lupus nephritis.

Few thoughts: Wonder how Rituximab affects basophils? If this is a possible mechanism, then every patient with Job Syndrome should get Lupus?


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