Polyvalent human immunoglobulin for infectious diseases: Potential to circumvent antimicrobial resistance.

Antimicrobial resistance (AMR) is a global health problem that causes more than 1.27 million deaths annually; therefore, it is urgent to focus efforts on solving or reducing this problem. The major causes of AMR are the misuse of antibiotics and antimicrobials in agriculture, veterinary medicine, and human medicine, which favors the selection of drug-resistant microbes. One of the strategies proposed to overcome the problem of AMR is to use polyvalent human immunoglobulin or IVIG. The main advantage of this classic form of passive immunization is its capacity to enhance natural immunity mechanisms to eliminate bacteria, viruses, or fungi safely and physiologically. Experimental data suggest that, for some infections, local administration of IVIG may produce better results with a lower dose than intravenous application. This review presents evidence supporting the use of polyvalent human immunoglobulin in AMR, and the potential and challenges associated with its proposed usage.

Oral Administration of Human Polyvalent IgG by Mouthwash as an Adjunctive Treatment of Chronic Oral Candidiasis.

Candida albicans is a commensal fungus that can cause disease ranging in severity from moderate to severe mucosal infections to more serious life-threating disseminated infections in severely immunocompromised hosts. Chronic mucocutaneous candidiasis (CMC) occurs in patients with mutations in genes affecting IL-17-mediated immunity, such as STAT3, AIRE, RORC, CARD9, IL12B, and IL12RB1, or gain of function (GOF) mutations in STAT1. New strategies for the treatment of candidiasis are needed because of the increased burden of infections and the emergence of drug-resistant strains. In this study, we investigated an aspect of the role of antibodies in the control of C. albicans infection. We tested in vitro the effects of C. albicans opsonization with commercial human polyvalent intravenous IgG (IV IgG) on NADPH oxidase activity and killing of the fungi by blood leukocytes from 11 healthy donors and found a significant enhancement in both phenomena that was improved by IV IgG opsonization. Then, we hypothesized that the opsonization of Candida in vivo could help its elimination by mucosal phagocytes in human patients with mucocutaneous candidiasis. We tested a novel adjunctive treatment for oral candidiasis in humans based on topical treatment with IV IgG. For this purpose, we choose two pediatric patients with well-characterized primary immunodeficiencies who are susceptible to CMC. Two 8-year-old female patients with an autosomal recessive mutation in the IL12RB1 gene (P1, with oral candidiasis) and a GOF mutation in STAT1 (P2, with severe CMC persistent since the age of 8 months and resistant to pharmacological treatments) were treated with IV IgG administered daily three times a day as a mouthwash over the course of 2 weeks. The treatment with the IV IgG mouthwash reduced C. albicans mouth infection by 98 and 70% in P1 and P2, respectively, after 13 days, and complete fungal clearance was observed after complementary nystatin and caspofungin treatments, respectively. Therefore, treatment of oral candidiasis with human polyvalent IgG administered as a mouthwash helps eliminate mucosal infection in humans, circumventing drug resistance, and opening its potential use in patients with primary or transient immunodeficiency.

Immunologic studies of specific mucosal and systemic immune responses in Mexican school children after booster aerosol or subcutaneous immunization with measles vaccine.

The purpose of the present study was to compare serum and mucosal immune responses following either aerosol (Aer) or subcutaneous (SQ) measles immunization of Mexican school children. A cohort of 49 children from 6 to 7 years of age received either Aer ( n = 22) or SQ ( n = 27) Edmonston-Zagreb (EZ) measles vaccine. Serum and nasal secretions were collected prior to (Pre), 1 and 3 months (mos) intervals and analyzed for immunoglobulin (Ig) concentrations and measles specific Ig isotype-associated antibody by enzyme immunoassay (EIA). Serum and nasal IgG and IgA antibody responses were stimulated following immunization with live, attenuated EZ measles vaccine administered either by SQ or Aer routes but these responses were significantly greater by the Aer compared to the SQ route. These studies also suggest that the level of antibody in these secretions may serve as an important marker of immunity to measles and lend further support for aerosol immunization as an effective alternative vaccine delivery strategy for measles eradication.

IgE and non-IgE food allergy.

BACKGROUND: Food allergy (FA) is characterized by an abnormal immunologic reactivity to food proteins. The gastro-intestinal tract serves not only a nutritive function but also is a major immunologic organ. Although previously thought to be triggered primarily by an IgE-mediated mechanism of injury, considerable evidence now suggests that non-IgE mechanisms may also be involved in the pathogenesis of FA. OBJECTIVE: To review the immunologic disturbances that occur in FA and to correlate these with the clinical manifestations expressed in affected target organs based upon a classification of IgE and non-IgE mechanisms. METHODS: Data collected from a computerized MEDLINE search were used for the analysis of the following topics: immediate GI hypersensitivity, oral allergy syndrome, acute urticaria and angioedema, acute bronchospasm, celiac disease, cow's milk enteropathy, dietary protein enterocolitis, breast milk colitis, proctolitis, proctitis, dermatitis herpetiformis, Heiner syndrome, eosinophilic gastroenteritis, atopic dermatitis, asthma, attention-deficit-hyperactivity disorder and behavioral disorders, as well as systems affected by mucosal associated lymphoid tissue-mediated injury of associated lymphoid tissues and the immunologic deviation to Th1 or Th2 mechanisms of FA. CONCLUSIONS: The results of this review allow the construction of a central, unifying hypothesis for a new classification of FA as follows: the clinical manifestations of FA, expressed in affected target organs, may be the result of immunologic injury mediated by interaction of food antigens with contiguous elements of mucosal associated lymphoid tissue. These appear to be modulated by relative imbalances of the Th1/Th2 paradigm, which may be the ultimate determinant governing the expression of FA as IgE-mediated, non--IgE-mediated, or mixed forms of IgE/non-IgE mechanisms of FA.