Special article
Hypothesis: dysregulation of immunologic balance resulting from hygiene and socioeconomic factors may influence the epidemiology and cause of glomerulonephritis worldwide

https://doi.org/10.1016/S0272-6386(03)00801-1Get rights and content

Abstract

Glomerular diseases show diverse epidemiological characteristics throughout the world, which has been suggested to be caused by differences in genetics of the underlying populations or environmental exposure to the putative antigens or agents that either trigger or induce the disease. Recently, an alteration in immune balance of the T helper 1 (TH1) and T helper 2 (TH2) subsets has been implicated as a mechanism to explain the relative increase in allergic diseases in industrialized nations. According to the Hygiene Hypothesis, overcrowding and poor hygiene early in life may protect from atopic diseases because exposure to microbes predisposes in favor of a TH1-dominant response. Conversely, dominance of the TH2 subset would be responsible for the increasing incidence of allergies. We present the hypothesis that this imbalance may help explain the predilection for membranoproliferative glomerulonephritis (GN) and mesangial proliferative GN to be associated with developing and/or poor nations, whereas immunoglobulin A nephropathy and minimal change disease are observed more commonly in industrialized nations. The implication of the Hygiene Hypothesis is that clinical expression of immune-mediated renal disease would depend on the prevailing TH1/TH2 balance, rather than the etiologic agent, and it may help explain the epidemiological pattern of glomerular diseases worldwide.

Section snippets

Cell-mediated immunity is regulated by T helper cell subsets

The immune system is controlled largely by T helper (TH) cells (CD4+ cells). The principal function of CD4+ cells expressing the TH1 phenotype is the immune response to infection. These cells are responsible for the induction of cell-mediated organ-specific immunity and the generation of complement-fixing antibody, and the process is orchestrated by the release of interleukin-12 (IL-12) from activated macrophages, interferon-γ (IFN-γ) from natural killer cells, and activation of CD4+ cells to

The Hygiene Hypothesis as a mechanism to explain the increasing frequency of allergies in industrialized nations

The Hygiene Hypothesis originally was proposed as a mechanism to explain the marked increase in allergies observed in industrialized (Westernized) societies.18, 19, 20, 21, 22, 23, 24, 25 Specifically, the hypothesis proposes that early and frequent exposure to bacterial and other antigens, common in developing nations, leads to a normal TH1 response, but that the better public hygiene and less infections observed in industrialized nations may lead to persistence of the TH2 phenotype and

Can the Hygiene Hypothesis explain the epidemiological patterns of glomerular disease observed worldwide?

Studies largely led by Holdsworth et al26 have shown that most proliferative glomerular diseases are driven by a TH1 response. One might then hypothesize that such diseases as MPGN, mesangial proliferative glomerulonephritis (GN; of the non-IgA type), and poststreptococcal GN may be more frequent in developing countries. MPGN is one of the most common glomerular diseases in Africa (such as Nigeria),3, 4 the West Indies (Trinidad),27 eastern Europe (Poland),28 Turkey,29 and east China.30 In

The renal Hygiene Hypothesis: summary, caveats, and future studies

To summarize, we propose a new hypothesis to explain the divergent epidemiological characteristics of glomerular disease worldwide. Specifically, we suggest that the overall hygiene and socioeconomic status of a country may predispose its citizens to either a TH1- or TH2-dominant phenotype that will increase the susceptibility of that population to specific types of glomerular disease. Although recognizing that true incidence data are lacking, we present evidence that TH1-dominant diseases,

Acknowledgements

The authors thank the following physicians for providing data on glomerular disease patterns in their respective countries: Dr E. Kasamatsu (Paraguay), Dr N. Mazzuchi (Uruguay), and Dr A. Pinto (Venezuela).

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