Antibody levels to tetanus, diphtheria, measles and varicella in patients with primary immunodeficiency undergoing intravenous immunoglobulin therapy: a prospective study

Abstract

BackgroundPatients with antibody deficiencies depend on the presence of a variety of antibody specificities in intravenous immunoglobulin (IVIG) to ensure continued protection against pathogens. Few studies have examined levels of antibodies to specific pathogens in IVIG preparations and little is known about the specific antibody levels in patients under regular IVIG treatment. The current study determined the range of antibodies to tetanus, diphtheria, measles and varicella in IVIG products and the levels of these antibodies in patients undergoing IVIG treatment.MethodsWe selected 21 patients with primary antibody deficiencies who were receiving regular therapy with IVIG. Over a period of one year, we collected four blood samples from each patient (every 3 months), immediately before immunoglobulin infusion. We also collected samples from the IVIG preparation the patients received the month prior to blood collection. Antibody levels to tetanus, diphtheria, measles and varicella virus were measured in plasma and IVIG samples. Total IgG levels were determined in plasma samples.ResultsAntibody levels to tetanus, diphtheria, varicella virus and measles showed considerable variation in different IVIG lots, but they were similar when compared between commercial preparations. All patients presented with protective levels of antibodies specific for tetanus, measles and varicella. Some patients had suboptimal diphtheria antibody levels. There was a significant correlation between serum and IVIG antibodies to all pathogens, except tetanus. There was a significant correlation between diphtheria and varicella antibodies with total IgG levels, but there was no significant correlation with antibodies to tetanus or measles.ConclusionsThe study confirmed the variation in specific antibody levels between batches of the same brand of IVIG. Apart from the most common infections to which these patients are susceptible, health care providers must be aware of other vaccine preventable diseases, which still exist globally.

International Consensus Document (ICON): Common Variable Immunodeficiency Disorders

“…Note also that the amount of antibody against these agents varies from product to product or from lot to lot and that caution regarding exposure is still advisable when patients live in or travel to areas where these diseases are still common. 216 Efficacy and safety of less frequently used live-agent vaccines have not been studied in patients with CVID, and they are usually considered to be contraindicated. The risk of transmission of routine (and other) live-agent vaccines is usually low, and therapeutic IgG is neutralizing for measles, mumps, rubella (MMR) and varicella vaccines, so they may be used routinely in family members of patients with CVID.…”

Protective Levels of Varicella-Zoster Antibody Did Not Effectively Prevent Chickenpox in an X-Linked Agammaglobulinemia Patient

“…However, it is well known that many factors may have an impact on the quality and quantity of antibodies in IVIG preparations, and there are differences in immunoglobulin content from brand to brand as well as from batch to batch 1 , 3 , 4 , 6 , 11 , 12 .…”

“…Patients who have immunodeficiency disorders rely on immunoglobulin prophylaxis to prevent common infectious diseases. Intravenous immunoglobulin (IVIG) products are prepared from pools of plasma collected from a large number of healthy donors and, therefore, contain antibodies against many infectious agents preventing a variety of bacterial and viral infections, such as varicella, in patients with impaired antibody production 1 , 4 , 12 .…”

Antibodies to vaccine antigens in pooled polyclonal human IgG products

“…Table presents data on antibodies to bacterial antigens from several studies of multiple lots of products produced in the US, UK, and EU . Antibodies against tetanus and diphtheria toxins are in the same range in 3 of the 4 studies which report them, but the results reported by Wu et al for products made from US source plasma seem to represent outliers, perhaps due to technical differences in the way the ELISAs were performed in that laboratory.…”