Oral administration of human serum immunoglobulin in immunodeficient patients with viral gastroenteritis. A pharmacokinetic and functional analysis.

Abstract

We examined the pharmacokinetics and immunological activity of human serum immunoglobulins (HSG) possessing anti-rotavirus activity which were orally administered to three children with primary immunodeficiency syndromes and prolonged gastrointestinal excretion of rotavirus. Detailed analysis of the excretion of immunoglobulins labeled with biotin or I"25 revealed that -50% of the recovered radioactivity was excreted in the stools over a 3-d period. Approximately half of the excreted radioactivity recovered in the stool was in a macromolecular form with immunological activity. The remainder of the recovered radioactivity was excreted in the urine as low molecular weight fragments or free iodide. In addition, immunological and chromatographic analyses revealed that the oral administration of HSG resulted in the generation of rotavirus-specific immune complexes in the gastrointestinal tract with a subsequent decrease in the presence of uncomplexed rotavirus antigen. These studies indicate that orally administered HSG can survive passage in the gastrointestinal tract in an immunologically active form, and that the oral administration of immunoglobulins with specific reactivities has potential for the prevention or treatment of gastrointestinal infections.

A Double-Blind, Placebo-Controlled Trial of Oral Human Immunoglobulin for Gastrointestinal Dysfunction in Children with Autistic Disorder

“…Additionally, there were no subjects with treatment-emergent serious AEs and only eight subjects discontinued the study due to AEs. These findings are in agreement with previous reports examining oral immunoglobulin in neonates (Barnes et al 1982) and children or adults with serious intestinal infections (Borowitz and Saulsbury 1991;Guarino et al 1994;Losonsky et al 1985;Tacket et al 1988;1992;Tjellstrom et al 1993Tjellstrom et al , 1997.…”

“…We can reasonably assume that the immunoglobulin was reaching the intestinal mucosa, as immunoglobulin has been shown to remain intact when administered orally Losonsky et al 1985;Tacket et al 1988). Thus, if the hypotheses were correct, we expected to see indications of a dose-response effect, even if the IgG survival rates were low.…”

“…Despite this controversy, there are claims of a specific GI immunopathology associated with autism that suggest treatments such as oral immunoglobulin, may prove to be effective in treating the GI dysfunction in children with autism (Borowitz and Saulsbury 1991;Guarino et al 1994;Losonsky et al 1985;Tacket et al 1988;1992;Tjellstrom et al 1993Tjellstrom et al , 1997. There is some evidence to support the use of oral immunoglobulin in other GI disorders, but in many of these disorders the etiology and pathophysiology are better characterized, such as rotavirus diarrhea, chronic diarrhea in children with short-gut syndrome, and pseudomembranous colitis due to Clostridium difficile.…”

“…The use of immunoglobulin has not been studied in well controlled trials in patients with IBS. Oral immunoglobulin appears to be well-tolerated with no serious side effects reported in low birth weight neonates (Barnes et al 1982), children and adults with serious intestinal infections (Borowitz and Saulsbury 1991;Guarino et al 1994;Losonsky et al 1985;Tacket et al 1988;1992;Tjellstrom et al 1993Tjellstrom et al , 1997, and in healthy adult volunteers (Bogstedt et al 1995). Schneider et al (2006) previously conducted an 8 week prospective open-label pilot study using oral immunoglobulin (Oralgam) in 12 children with autism and persistent GI dysfunction.…”

Gut mucosa barrier preservation by orally administered IgA-IgG to patients undergoing bone marrow transplantation: a randomised pilot study

“…In clinical trials the oral administration of several different immunoglobulin preparations has revealed that it can survive passage through the gastrointestinal tract of bone marrow transplantation recipients 5 and has protective effects against infectious diarrhoea and necrotizing enterocolitis. [6][7][8][9] It may be anticipated that production and function of IgA in the gastro-intestinal tract is disrupted by the preparative regimen preceding BMT. The aim of this placebo-controlled, randomised trial was therefore to investigate whether the oral administration of an IgA-IgG preparation made from human serum would reduce gastro-intestinal toxicity or infectious complications related to autologous BMT.…”