Jejunal mucosal enzyme activities, regulatory peptides and organelle pathology of the enteropathy of common variable immunodeficiency.

Abstract

SUMMARY Jejunal biopsies from six patients having the small bowel enteropathy associated with common variable immunodeficiency have been subjected to analytical subcellular fractionation and enzymic and regulatory peptide microassay to define the organelle pathology of this syndrome. Compared with normal subjects, the immunodeficient patients had decreased activities of the three brush border enzymes: alkaline phosphatase, y-glutamyl transferase and aglucosidase. The other organelle marker enzyme activities and all the regulatory peptide concentrations did not differ from the controls. Density gradient experiments showed a complete loss of particulate 3-glucosidase (lactase) with activity entirely located in the cytosol. The integrity of other organelles was normal. These data indicate that the enteropathy of common variable immunodeficiency is associated with abnormalities in the jejunal brush border analogous to those present in tropical malabsorption syndrome.Gastrointestinal symptoms are found in up to 60% of patients with common variable immunodeficiency (idiopathic acquired hypogammaglobulinaemia).l The cause of these symptoms is probably multifactorial but malabsorption is often prominent and certain jejunal histological abnormalities have been described and compared with those found in coeliac disease and tropical malabsorption.2-4 The biochemical abnormalities found in the mucosa in these two diseases are, however, distinct, probably reflectin the different pathogenesis of the mucosal damage. Furthermore, the mucosal regulatory peptides show characteristic abnormalities in these two forms of enteropathies.8 9 There are, however, no reports of investigations into the pathogenesis of the enteropathy of common variable immunodeficiency at the cellular and subcellular level. In this study we have assayed the mucosal enzyme activities and regulatory peptide concentrations and investigated the intracellular organelles in the jejunum from six patients with common variable immunodeficiency undergoing investigation for profuse diarrhoea.

Impaired nutritional status in common variable immunodeficiency patients correlates with reduced levels of serum IgA and of circulating CD4+ T lymphocytes

“…Mean pre-infusion serum IgG levels were 5971 63 mg dL 21 . Serum IgM was , 10 mg dL 21 in all subjects.…”

“…In fact, although substitution therapy with IVIg has markedly improved the quality of life of CVI patients during the last two decades, the incidence of recurrent infections and of co-morbid conditions (mainly of the GI tract) is still far higher than in the general population [7,21]. In fact, although substitution therapy with IVIg has markedly improved the quality of life of CVI patients during the last two decades, the incidence of recurrent infections and of co-morbid conditions (mainly of the GI tract) is still far higher than in the general population [7,21].…”

“…Patients with CVI are, at least theoretically, naturally prone to develop PCM. In fact, although substitution therapy with IVIg has markedly improved the quality of life of CVI patients during the last two decades, the incidence of recurrent infections and of co-morbid conditions (mainly of the GI tract) is still far higher than in the general population [7,21]. The presence of recurrent infections is known to be associated with a series of metabolic events leading to a state of negative nitrogen balance and significant loss of lean body mass with nutritional depletion: marked anorexia, net whole body protein breakdown and liver anabolism.…”

“…Common variable immunodeficiency (CVI) is a heterogeneous group of primary disorders of the immune system, characterized by decreased immunoglobulin synthesis and low serum immunoglobulin levels [mean serum immunoglobulin G (IgG) , 300 mg dL 21 , with reduction of IgM and/or IgA]. In some cases, abnormalities of the T-cell number and/or function are also detectable [1].…”

Evaluation of malnutrition risk and nutrition status in adult patients with common variable immunodeficiency

“…20,21 Although life expectancy is improved, the incidence of recurrent infections and concomitant diseases (especially the gastrointestinal system) is higher than in the general population. 22,23 Therefore, patients with CVID are at risk for malnutrition because of recurrent infections, malabsorption due to accompanying gastrointestinal diseases, and nutrition deficiency.…”