Microsoft Word - NEF422BF.rtf

Dr. E. Nigel Wardle, MD, ‘Greenways’, 21 Common Road, North Leigh, Oxon OX8 6RD (UK) Minimal change nephrotic syndrome (MCN) has proved so far to be an enigma. The prescribed treatment amounts to a trial of corticosteroid therapy [1,2] with the addition of cyclophosphamide for those who continue to relapse. Not surprisingly there are dissenting voices in respect of the steroid dosage schedule [3], and its duration [4, 5], and with regard to the ready use of cyclophosphamide [3]. Many, if not all, of these cases are associated with atopy [6]. Once the patient is receiving steroid therapy, this is an aspect that is difficult to investigate. There are good reports of the association of MCN in children with cow’s milk allergy. There is improvement on withdrawal of the offending food [7, 8]. MCN can be associated with allergy to eggs [8] or pork [9], or inhaled pollen [10] or house dust [11]. The serum IgE can be raised [12], in spite of proteinuria, and the basophil degranulation test for allergens has yielded useful data [13]. Discussions of the immunological background have progressed from details of lymphocyte subsets [14] to acceptance of the fact that a vascular permeability-inducing cytokine [15] must be implicated. So there has been focus on tumour necrosis factor [16] and vascular endo-thelial growth factor. We are still not sure of the mediator. Meantime one has begun to realize that division of helper T lymphocytes into Th-1 and Th-2 varieties, as was described in mice in the 1980s, is applicable to man. Thus in proliferative and progressive nephritides, in which a delayed hypersensitivity reaction accompanied by macro-phages is taking place in the glomeruli [17], the associated lymphocytes are of the Th1 type and they are producing interleukin (IL)-2 and interferon-γ (IFN-γ) [18]. There is accompanying complement activation and production if IgG2a and IgG3 antibodies. The reaction is the same as that used in the defence against bacteria, viruses and fungi, or intracellular parasites. On the other hand, if there are Th-2 helper lymphocytes producing the cytokines IL-4, IL-5 and IL-6, there is a long-lasting antibody response with production of IgE and IgG4 antibodies. This is the situation in allergic reactions and when there has to be defence against helminth parasites. When cytokine analyses are performed on the superna-tants of culture lymphocytes from grass pollen-allergic subjects to which grass pollen has been added, one can distinguish lymphocytes of allergic persons by their high production of IL-4 in relation to IFN-γ [ 19]. So one knows that these are Th-2 cells. As a result of many studies like this, one now realizes that allergy occurs in those persons who in early infancy have lymphocytes that produce little IFN-γ [20]. Clearly this approach should be useful in the study of patients with MCN. Initial studies from Seoul, Korea [21] revealed that B cells of children with MCN express increased membrane