A systematic literature review of the effects of immunoglobulin replacement therapy on the burden of secondary immunodeficiency diseases associated with hematological malignancies and stem cell transplants.

INTRODUCTION: Secondary immunodeficiency diseases (SID) caused by hematological malignancies (HMs), stem cell transplant (SCT), and associated therapies are mainly characterized by the presence of hypogammaglobulinemia or antibody production deficits. AREAS COVERED: The authors summarized the scientific literature on disease burden of SIDs in patients who had HMs or SCT. Systematic searches were conducted to identify English-language articles from 1994-2020, reporting on clinical, humanistic, and economic burdens of SID due to HMs or SCT. Definitions of SID and serum immunoglobulin G thresholds varied across 24 eligible studies. In most (n = 16) studies, patients received immunoglobulin replacement therapy (IGRT). Several studies found IGRT was associated with significant reductions in rates of infection and antimicrobial use. However, 1 study found no statistically significant difference in antibiotic use with IGRT. Only 3 studies reported on quality of life, and no economic studies were identified. EXPERT OPINION: Overall, the findings show several beneficial effects of IGRT on clinical outcomes and quality of life; however, disparate definitions, infrequent reporting of statistical significance, and scarcity of clinical trial data after the 1990s present areas for further investigation. This paucity indicates an unmet need of current evidence to assess the benefits of IGRT in SID.

Immunoregenerative effects of the bionically cultured Sanghuang mushrooms (Inonotus sanghuagn) on the immunodeficient mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Description of the pharmacological activities of Sanghuang mushrooms (Inonotus Sanghuang) can be traced back to Tang dynasty of China 1300 years ago. This mushroom has been widely accepted in China, Japan, Korea and certain regions of Europe as a nutraceutical medicine for enhancing immunity or an alternative medicine for prevention or inhibition of tumorigenesis. However, this mushroom is rarely available from the mulberry trees in the wild because of the rigorous conditions needed for formation of the Sanghuang mushrooms. AIM OF THE STUDY: This study aims to establish a practical protocol for culture, particularly for a bunch of production of Sanghuang mushrooms possibly to commercialize the cultured Sanghuang based on deep comparison of quality and pharmacological activities between the cultured and the wild Sanghuang. MATERIALS AND METHODS: A phylogenetic tree containing five strains of the wild Sanghuang was constructed using rDNA markers. Different temperatures and medium compositions were surveyed to develop a practical protocol for culture of the Sanghuang mushrooms. 5-fluorouracil was used to induce the immunodeficient mice. Chemotherapeutic components and pharmacological activities were deeply analyzed between a cultured strain (SG) and three strains of the wild Sanghuang. RESULTS: Maintenance of a temperature of 22-28 °C and a high relative humidity of 90-95%, and use of a high ratio (80%) of mulberry tree sticks in the medium were critical to successful culture of Sanghuang. The cultured mushrooms were yellow with a uniform shape, while the wild Sanghuang was dark brown with a smaller and irregular shape. The cultured mushrooms contained significantly higher levels of polysaccharides, amino acids, and water-soluble nutraceuticals, whereas flavones in the wild Sanghuang were significantly higher (P < 0.05). Use of a dose of 8 mg/kg or 16 mg/kg to immunoregenerate the immunodeficient mice was comparable between the cultured and wild Sanghang based on analysis of hematological parameters and histological examination of the thymus and spleen in the treated mice. CONCLUSIONS: This study highlights the potential of the immunoregenerative functions of the cultured Sanghuang for cancer chemotherapy and suggests that the cultured Sanghuang can be an alternative to wild Sanghuang used for nutraceutical medicine.

Deployment of Transchromosomal Bovine for Personalized Antimicrobial Therapy.

For decades, intravenous immunoglobulin (IVIg) has provided safe and effective therapy for immunodeficient patients. This proof-of-principle study describes a novel approach to generate personalized IVIg for chronic, antibiotic-resistant infection in real time.

Gene Therapy Approaches to Immunodeficiency.

Transfer of gene-corrected autologous hematopoietic stem cells in patients with primary immunodeficiencies has emerged as a new therapeutic approach. Patients with various conditions lacking a suitable donor have been treated with retroviral vectors and a gene-addition strategy. Initial promising results were shadowed by the occurrence of malignancies in some of these patients. Current trials, developed in the last decade, use safer viral vectors to overcome the risk of genotoxicity and have led to improved clinical outcomes. This review reflects the progresses made in specific disorders, including adenosine deaminase deficiency, X-linked severe combined immunodeficiency, chronic granulomatous disease, and Wiskott-Aldrich syndrome.

Pulmonologist perspectives regarding diagnosis and management of primary immunodeficiency diseases.

BACKGROUND: The time from symptom onset to diagnosis for patients with primary immunodeficiency diseases (PIDD) is an average of 12 years, but prompt diagnosis and treatment can promote best outcomes. OBJECTIVE: Because the manifestations of PIDD are often sinopulmonary in nature, patients with undiagnosed PIDD are frequently referred to pulmonologists. This study sought to identify opportunities among these specialists to improve diagnosis and clinical management of patients with PIDD. METHODS: A survey was sent to American Medical Association and American Osteopathic Association members whose specialty was pulmonology. Responses were compared with those from a historical survey of 71 subspecialist immunologists (American Academy of Allergy, Asthma Immunology members who devoted 10% of their practice to patients with PIDD). RESULTS: The surveys were returned by 485 pulmonologists, 49% of whom had diagnosed at least one patient with PIDD. In comparison with subspecialist immunologists, fewer pulmonologists were aware of the professional PIDD diagnosis and management guidelines and fewer followed up patients with various PIDDs. Pulmonologists and subspecialist immunologists also differed in the practice of prescribing prophylactic antibiotics and immunoglobulin replacement and in avoiding live viral vaccines. CONCLUSION: Differences in the diagnosis and treatment of patients with PIDD between these two groups of specialists revealed areas in which PIDD-focused educational initiatives may be helpful for pulmonologists.

Primary Immunodeficiency Diseases: An Opportunity in Pediatrics for Improving Patient Outcomes.

OBJECTIVES: Primary immunodeficiency diseases (PIDDs) are caused by inherent deficits in immune defenses that result in abnormal susceptibility to infection. In most cases, early and appropriate diagnosis can improve patient outcomes. The objective of this study was to evaluate understanding, recognition, and diagnosis of PIDD among pediatricians. METHODS: A mail survey sent to a sample of pediatricians obtained from the American Medical Association and American Osteopathic Association. Results were compared with a similar survey of specialists who are members of the American Academy of Asthma, Allergy and Immunology. RESULTS: More than a third (35%) of pediatricians were uncomfortable with the recognition and diagnosis of PIDD despite 95% having ordered screening tests or referring patients to specialists to be evaluated for PIDD, and 77% having followed at leastone patient with PIDD. In all, 84% of pediatricians were unaware that professional guidelines for PIDD exist. CONCLUSIONS: Patients with PIDD would benefit from improved recognition of the diseases by pediatricians in order to facilitate earlier diagnosis and optimize ongoing therapy.

Primary Immune Deficiency Treatment Consortium (PIDTC) report.

The Primary Immune Deficiency Treatment Consortium (PIDTC) is a network of 33 centers in North America that study the treatment of rare and severe primary immunodeficiency diseases. Current protocols address the natural history of patients treated for severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome, and chronic granulomatous disease through retrospective, prospective, and cross-sectional studies. The PIDTC additionally seeks to encourage training of junior investigators, establish partnerships with European and other International colleagues, work with patient advocacy groups to promote community awareness, and conduct pilot demonstration projects. Future goals include the conduct of prospective treatment studies to determine optimal therapies for primary immunodeficiency diseases. To date, the PIDTC has funded 2 pilot projects: newborn screening for SCID in Navajo Native Americans and B-cell reconstitution in patients with SCID after hematopoietic stem cell transplantation. Ten junior investigators have received grant awards. The PIDTC Annual Scientific Workshop has brought together consortium members, outside speakers, patient advocacy groups, and young investigators and trainees to report progress of the protocols and discuss common interests and goals, including new scientific developments and future directions of clinical research. Here we report the progress of the PIDTC to date, highlights of the first 2 PIDTC workshops, and consideration of future consortium objectives.

Stem cell transplantation for primary immune deficiency.

PURPOSE OF REVIEW: In this article, we summarize the recent advances in treating primary immune deficiency (PID) disorders by stem cell transplantation (SCT); we have focused on articles published in the past 2 years since the last major review of SCT for PID. RECENT FINDINGS: Analyses of the outcomes of SCT for PID by specific molecular defect have clarified which conditions are receptive to unconditioned transplants and which require more myeloablative conditioning. Improved outcomes for 'difficult' conditions [adenosine deaminase-severe combined immunodeficiency (ADA-SCID), major histocompatibility complex class II deficiency] and potential advantages of using cord blood as a stem cell source have also been described. Newborn screening for SCID identifies well babies with SCID: the optimal SCT protocol for such young infants remains to be determined. Reduced toxicity conditioning has been successfully used to treat conditions such as Wiskott-Aldrich syndrome and chronic granulomatous disease, offering curative engraftment with reduced transplant-related mortality. Similarly, treating children with familial hemophagocytic lymphohistiocytosis using reduced intensity conditioning SCT results in much improved outcomes. Advances in next generation sequencing have identified new diseases amenable to SCT, such as DOCK8 deficiency, resulting in improved quality of life and protection from malignancy. SUMMARY: Recent studies suggest that further improvements in treating PID with SCT are possible with a greater understanding of the genetics and immunobiology of these diseases, facilitating the matching of donor type and conditioning regimens, or indeed alternative therapies (such as gene therapy) to specific PID disorders.

[Composition and clinical use of bovine colostrums].

In recent years, a large number of the researches giving fuller picture about structure and properties of bovine colostrums (BC), that allows to apply it at various diseases in clinical practice was carried out in the world. The critical analysis of the modern literature showed bovine colostrums is rich with immunoglobulins, antimicrobials and growth factors in comparison with nature milk. The positive effect of supplementation of bovine colostrums in diarrhea in persons with immune-deficiency syndromes, for treatment NSAID-induced gastrointestinal disturbances, at postoperative responses and in treatment of upper respiratory infection is supposed.

Efecto inmunomodulador de la ozonoterapia en niños con deficiencia en la inmunidad mediada por fagocitos / Immunomodulator effect of ozone therapy in children with deficiency in immunity mediated by phagocytes

Se realizó un estudio pre-experimental antes después, con la finalidad de evaluar el efecto inmunomodulador de la ozonoterapia en niños con inmunodeficiencia por defectos en la inmunidad mediada por fagocitos. El universo estuvo constituido por un total de 18 niños con deficiencias en la fagocitosis, asistidos en la consulta de Inmunología en el periodo desde septiembre de 2009 hasta junio de 2010, que cumplieron con los criterios de inclusión y exclusión. El ozono se aplicó en dosis escalonadas por insuflación rectal hasta una concentración de 40µg/mL, durante tres meses. Las variables fueron evaluadas 1 mes después del tratamiento. Se determinó si existen diferencias significativas entre las determinaciones antes y después de la ozonoterapia, mediante la prueba T de comparación de medias para muestras dependientes, con un nivel de significación α=0.05. Hubo aumentos significativos del conteo absoluto de neutrófilos en el 100 por ciento de los casos y en el 94 por ciento mejoró significativamente la función fagocítica leucocitaria después de recibir la ozonoterapia. El estado clínico, cualitativamente evaluado, fue satisfactorio en los niños tratados con Ozono y no se reportaron reacciones adversas durante el tratamiento. Se sugiere este proceder terapéutico como alternativa terapéutica inmunoestimulante en la deficiencia fagocítica(AU)

A pre-experimental study was conducted before then, in order to assess the effect of immunomodulator of ozone therapy in children with immunodeficiency defects of phagocyte-mediated immunity. The universe was made up by a total of 18 children with deficiencies in phagocytosis, assisted in the Immunology consultation from September 2009 until June 2010 that met the inclusion and exclusion criteria. Ozone was applied in doses by rectal insufflation stepped up a 40µg/mL concentration, for three months. The variables were assessed 1 month after treatment. It was determined if there are significant differences between determinations before and after of ozone therapy, through T of means comparison test for dependent samples, with a significance level α = 0. 05. There were significant increases in the absolute neutrophil count in 100 percent of cases and the Leukocyte Phagocytic function significantly improved in a 94 percent after receiving ozone therapy. The clinical state, qualitatively evaluated, was satisfactory in children treated with ozone and no adverse reactions were reported during treatment. It is suggested this therapeutic approach as immunostimulant therapeutic alternative in the phagocytic deficiency(AU)

Efecto inmunomodulador de la ozonoterapia en niños con deficiencia en la inmunidad mediada por fagocitos / Immunomodulator effect of ozone therapy in children with deficiency in immunity mediated by phagocytes

Se realizó un estudio pre-experimental antes después, con la finalidad de evaluar el efecto inmunomodulador de la ozonoterapia en niños con inmunodeficiencia por defectos en la inmunidad mediada por fagocitos. El universo estuvo constituido por un total de 18 niños con deficiencias en la fagocitosis, asistidos en la consulta de Inmunología en el periodo desde septiembre de 2009 hasta junio de 2010, que cumplieron con los criterios de inclusión y exclusión. El ozono se aplicó en dosis escalonadas por insuflación rectal hasta una concentración de 40µg/mL, durante tres meses. Las variables fueron evaluadas 1 mes después del tratamiento. Se determinó si existen diferencias significativas entre las determinaciones antes y después de la ozonoterapia, mediante la prueba T de comparación de medias para muestras dependientes, con un nivel de significación α=0.05. Hubo aumentos significativos del conteo absoluto de neutrófilos en el 100 por ciento de los casos y en el 94 por ciento mejoró significativamente la función fagocítica leucocitaria después de recibir la ozonoterapia. El estado clínico, cualitativamente evaluado, fue satisfactorio en los niños tratados con Ozono y no se reportaron reacciones adversas durante el tratamiento. Se sugiere este proceder terapéutico como alternativa terapéutica inmunoestimulante en la deficiencia fagocítica.

A pre-experimental study was conducted before then, in order to assess the effect of immunomodulator of ozone therapy in children with immunodeficiency defects of phagocyte-mediated immunity. The universe was made up by a total of 18 children with deficiencies in phagocytosis, assisted in the Immunology consultation from September 2009 until June 2010 that met the inclusion and exclusion criteria. Ozone was applied in doses by rectal insufflation stepped up a 40µg/mL concentration, for three months. The variables were assessed 1 month after treatment. It was determined if there are significant differences between determinations before and after of ozone therapy, through T of means comparison test for dependent samples, with a significance level α = 0. 05. There were significant increases in the absolute neutrophil count in 100 percent of cases and the Leukocyte Phagocytic function significantly improved in a 94 percent after receiving ozone therapy. The clinical state, qualitatively evaluated, was satisfactory in children treated with ozone and no adverse reactions were reported during treatment. It is suggested this therapeutic approach as immunostimulant therapeutic alternative in the phagocytic deficiency.

Use of intravenous immunoglobulin and adjunctive therapies in the treatment of primary immunodeficiencies: A working group report of and study by the Primary Immunodeficiency Committee of the American Academy of Allergy Asthma and Immunology.

There are an expanding number of primary immunodeficiency diseases (PIDDs), each associated with unique diagnostic and therapeutic complexities. Limited data, however, exist supporting specific therapeutic interventions. Thus, a survey of PIDD management was administered to allergists/immunologists in the United States to identify current perspectives and practices. Among 405 respondents, the majority of key management practices identified were consistent with existing data and guidelines, including the provision of immunoglobulin therapy, immunoglobulin dosing and selective avoidance of live viral vaccines. Practices for which there are little specific data or evidence-based guidance were also examined, including evaluation of IgG trough levels for patients receiving immunoglobulin, use of prophylactic antibiotics and recommendations for complementary/alternative medicine. Here, variability applied to PIDD patients was identified. Differences between practitioners clinically focused upon PIDD and general allergists/immunologists were also identified. Thus, a need for expanded clinical research in PIDD to optimize management and potentially improve outcomes was defined.

Evaluación de la respuesta inmune celular de pacientes inmunodeprimidos tratados con inmunoestimulantes, suplementos vitamínicos y oligoelementos / Evaluation of the immune cellular response of immunodepressed patients treated with immunostimulants, vitamin supplements and olygoelements

Se realizó un análisis para demostrar la importancia que tiene la combinación del tratamiento específico con el tratamiento de apoyo nutricional en el caso de las inmunodeficiencias. Se trata de un estudio prospectivo y descriptivo de 40 pacientes inmunodeficientes celulares y con deficiencia en el mecanismo de la fagocitosis, a quienes se les evaluó la evolución clínica después del tratamiento impuesto. Los pacientes fueron monitoreados con la prueba de roseta espontánea y activa y con el índice opsonofagocítico antes y después del tratamiento, el cual tuvo una duración variable entre 3-5 meses. El tratamiento consistió en la administración de un inmunoestimulante (levamisol, factor de transferencia e inmunoferón), suplementos vitamínicos y oligoelementos. Para el procesamiento estadístico se realizó la prueba de t pareada, donde se apreció una diferencia significativa entre las mediciones antes y después del tratamiento en la muestra estudiada. En todos los pacientes se elevó la inmunidad, lo cual les permitió buena respuesta ante las infecciones(AU)

An analysis was made to show the importance of the combination of the specific treatment with the nutritional supplement therapy in the specific case of immunodeficiencies. A prospective and descriptive study of 40 cellular immunodeficient patients with deficiency in the phagocytosis mechanism was conducted. Their clinical evolution after treatment was assessed. The patients were monitored with the spontaneous and active rosette test and with the opsonophagocytic index before and after treatment, which lasted between 3 and 5 months. The treatment consisted in the administration of an immunostimulant (levamisol, transference factor and immunoferon), vitamin supplements and olygoelements. The paired t test was performed for the statistical processing, where a significant difference between the measurements before and after the treatment was observed in the studied sample. Immunity increased in all patients, which allowed them to have a good response to infection(AU)

Haemopoietic stem cell transplantation for genetic disorders.

Stem cell transplantation (SCT) is used to cure or greatly ameliorate a wide variety of genetic diseases, ranging from inherent defects of haemopoietic cell production or function to metabolic diseases mostly affecting solid organs. It ranks as one of the most remarkable therapeutic advances of the past 40 years. Despite rapid technological improvements, however, there are still many short term risks and potential long term toxicities. As a consequence, the rapid emergence of alternative therapies (including new drugs, enzyme and gene therapies), necessitate constant re-evaluation of the risk/benefit ratio for each disease and hence the appropriateness of SCT. This review describes the major aspects of the transplant process, indications for transplantation, outcome statistics, and areas where alternative therapies are becoming available.

[Enterosorption and nutritious support with pectin-containing preparation in the treatment of stress immunodeficiency in peritonitis].

Fifty-eight patients aged from 18 to 65 years with peritonitis of different etiology in toxic and terminal phases were treated. Nasoenteral intubation, enterosorption and early nutritious support with pectin-containing preparation (PCP) were carried out in all the patients just after surgery with standard course of 5 days. Baseline data was compared with that after PCP-supported treatment. Powder products of red beet were used as PCP. Immunodeficiency in peritonitis is characterized by imbalance of stress-realizing and stress-limiting mechanisms of immunocompetent cells. Enterosorption and early nutritious support with PCP in peritonitis decrease the level of plasmic cortisol and enhance stress-limiting reception that reduces a harmful effect of cortisol and reestablishes immunity.

Evolución clínica de pacientes tratados con factor de transferencia / Clinical evolution of patients treated with transfer factor

La efectividad del factor de transferencia no ha sido evaluada en investigaciones poscomercialización. Realizamos un estudio transversal y descriptivo en 9 hospitales de Ciudad de La Habana, desde abril del 2001 hasta abril del 2002, para evaluar la evolución clínica de 280 pacientes tratados con este inmunoestimulante. Se midió el número de recurrencias de la enfermedad presentadas un año antes y las observadas un año después del tratamiento. Además, se obtuvo información sobre esquema terapéutico, motivos de prescripción y pruebas inmunológicas realizadas antes y después del tratamiento. La evolución fue satisfactoria en el 43,6 por ciento, parcialmente satisfactoria en el 39,4 por ciento e insatisfactoria en el 16,3 por ciento. Solo en el 41,8 por ciento se realizó un estudio complementario previo a la prescripción, a ninguno se le realizó después. El tratamiento con factor de transferencia mejoró la evolución clínica de los pacientes estudiados, aunque en todos los casos no se confirmó una inmunodeficiencia celular(AU)

Evolución clínica de pacientes tratados con factor de transferencia / Clinical evolution of patients treated with transfer factor

La efectividad del factor de transferencia no ha sido evaluada en investigaciones poscomercialización. Realizamos un estudio transversal y descriptivo en 9 hospitales de Ciudad de La Habana, desde abril del 2001 hasta abril del 2002, para evaluar la evolución clínica de 280 pacientes tratados con este inmunoestimulante. Se midió el número de recurrencias de la enfermedad presentadas un año antes y las observadas un año después del tratamiento. Además, se obtuvo información sobre esquema terapéutico, motivos de prescripción y pruebas inmunológicas realizadas antes y después del tratamiento. La evolución fue satisfactoria en el 43,6 por ciento, parcialmente satisfactoria en el 39,4 por ciento e insatisfactoria en el 16,3 por ciento. Solo en el 41,8 por ciento se realizó un estudio complementario previo a la prescripción, a ninguno se le realizó después. El tratamiento con factor de transferencia mejoró la evolución clínica de los pacientes estudiados, aunque en todos los casos no se confirmó una inmunodeficiencia celular