Secondary Immunodeficiency Disorders Research Articles

Immunodeficiency: Burden of Illness.

Immunodeficiency disorders pose substantial burdens on the health-care system and the patients affected. Broadly, immunodeficiencies can be divided into primary immunodeficiency disorders (PIDDs) and secondary immunodeficiency disorders. This review will focus on PIDDs. The overall prevalence for PIDDs is estimated to be ∼1-2% of the population but may be underestimated due to underdiagnosis of these conditions. PIDDs affect males slightly more often than females. The mortality rates differ based on the specific condition but can be extremely high if the condition is left undiagnosed or untreated. The most common causes of death are infections, respiratory complications, and cancers (e.g., lymphoma). Comorbidities and complications include infection, chronic lung disease, granulomatous lymphocytic interstitial lung disease, and autoimmune disorders. The disease burden of patients with common variable immunodeficiency (CVID) is estimated to be greater than patients with diabetes mellitus and chronic obstructive pulmonary disease. PIDDs have a serious impact on the quality of life of the patients, including sleep disturbance, anxiety, and social participation as well as other psychosocial burdens associated with these disorders. The financial cost of PIDDs can be substantial, with the cost of untreated CVID estimated to be $111,053 per patient per year. Indirect costs include productivity loss and time lost due to infusion and hospital visits. Secondary immunodeficiency is not fully discussed in this review but likely contributes equally to the burden of overall immunodeficiency disorders. Management of patients with PIDDs should use a comprehensive approach, including medical, nursing, psychiatric, and quality of life, to improve the outcome.

Access and use of immunoglobulins in supportive cancer care: A thematic analysis of a systematic review data set.

Secondary immunodeficiency (SID) disorders are known to occur in patients with haematological malignancies (HM) due to immunosuppressive treatments. Recurring infections causing subsequent morbidity and mortality commonly occur in this patient cohort. Immunoglobulin replacement therapy (IgRT) benefits patients with primary antibody deficiencies. However, evidence supporting their therapeutic role is not as explicit in SID-associated antibody deficiencies, which raises the questions regarding its use in SID and the knock-on effects of this use on its access and availability more generally. This study aimed to learn about the use of immunoglobulins in SID, identify themes concerning its use and access and suggest methods for improving access. This study included a thematic analysis of a published data set of 43 articles concerning immunoglobulin use and access in SID. The data set used to perform the thematic analysis is based on research articles identified from Excerpta Medica Database (EMBASE) and PubMed databases, published as part of a systematic review and part 1 of this two-part publication series. A thematic synthesis was conducted to identify recurrent themes. The three primary themes included (1) the context for IgRT prescription, which included patient characteristics and cost burden of IgRT administration, and its use in different countries; (2) factors contributing to inappropriate IgRT use, including health care professionals' awareness of IgRT, disparity between guidelines and actual clinical practice, and the effect of shortages on prescription and chemotherapy-induced hypogammaglobulinemia (HGG); and (3) measures identified to improve IgRT use and access, which included multidisciplinary involvement, improved diagnostic tools and safer withdrawal and stewardship protocols. IgRT use is increasing in HM as a supportive therapy but without comprehensive clinical guidelines and appropriate prescribing recommendations, medication wastage may occur with consequences for immunoglobulin access.

Outcomes of COVID-19 in immunocompromised patients: a single center experience.

Malignancy, bone marrow and organ transplantation are associated with deficient and defective immune systems. Immunocompromised patients are at risk for severe and chronic complication of COVID-19 infection. However, the pathogenesis, diagnosis and management of this comorbidity remain to be elucidated. The purpose of the present study was to describe key aspects of COVID-19 infection in immunocompromised patients. In this retrospective, cross-sectional study, lab findings and outcomes of 418 COVID-19 patients with secondary immunodeficiency disorders admitted to Taleghani Hospital in Tehran, from March 2020 to September 2022 were investigated.Of the 418 immunocompromised patients with COVID-19, 236 (56.5%) ‌ were male and the median age of all studied patients was 56.6 ± 16.4 with range of 14 to 92 years. Totally, 198 (47.4%) of the patients died during hospitalization. Remdesivir was used for treatment of all patients. Mortality rate among patients admitted to ICU ward (86.8%) was significantly higher than non ICU admission (p < 0.001). The death rate in patients with CKD was substantially higher than other underlying disease (p < 0.001). In terms of laboratory finding, there was a significant relationship between ICU admission and worse outcome with WBC count (HR = 1.94, 95% CI = 1. 46-2.59, p < 0.001), PMN count (HR = 1.93, 95% CI = 1.452.56, p < 0.001), Hb (HR = 1.49, 95% CI = 1.042.13, p = 0.028), AST (HR = 2.55, 95% CI = 1.913.41, p < 0.001), BUN (HR = 2.56, 95% CI = 2.063.69, p < 0.001), Cr (HR = 2.63, 95% CI = 1.89-3.64, p < 0.001), Comorbidities index (HR = 1.71, 95% CI = 1.29-2.27, p < 0.001) and aging (HR = 1.91, 95% CI = 1.4-2.54, p < 0.001).Immunocompromised status increased the risk of mortality or worse outcome in patients diagnosed with COVID-19. Our finding showed outcome predicting markers in whom the waned immune system encounter new emerging disease and improved our understanding of COVID-19 virus behavior in immunocompromised individuals.

HIV infection in the practice of a family doctor and the possibility of AIDS therapy

AIDS, or acquired immunodeficiency syndrome, was originally defined by the Centers for Disease Control as "the presence of a reliably diagnosable disease in which there is at least a mild defect in cell-mediated immunity". The modern definition includes the presence of a group of various disorders caused by opportunistic flora, diagnosed presumably or definitively in individuals with laboratory-proven HIV infection in the absence of other reliable causes of immunodeficiency. From a practical standpoint, the clinician should consider HIV infection as a spectrum of disorders ranging from primary infection, with or without acute HIV syndrome, and asymptomatic infection to overt disease. This article is devoted to the issues of classification, clinical symptoms, and approaches to the diagnosis and treatment of secondary immunodeficiency disorders on the example of AIDS caused by the human immunodeficiency virus (HIV).

British Society for Immunology and United Kingdom Primary Immunodeficiency Network (UKPIN) consensus guideline for the management of immunoglobulin replacement therapy.

SummaryCurrently, there is no guideline to support the use of immunoglobulin replacement therapy (IgRT) in primary and secondary immunodeficiency disorders in UK. The UK Primary Immunodeficiency Network (UK-PIN) and the British Society of Immunology (BSI) joined forces to address this need. Given the paucity of evidence, a modified Delphi approach was used covering statements for the initiation, monitoring, discontinuation of IgRT as well as home therapy programme. A group of six consultant immunologists and three nurse specialists created the statements, reviewed responses and feedback and agreed on final recommendations. This guideline includes 22 statements for initiation, 22 statements for monitoring, 11 statement for home therapy, and 19 statements for discontinuation of IgRT. Further areas of research are proposed to improve future delivery of care.

Clinical Outcomes of COVID-19 in Common Variable Immunodeficiency Patients

Patients with primary and secondary immunodeficiency disorders are at increased risk of worse outcomes in coronavirus disease 2019 (COVID-19). We describe clinical outcomes of COVID-19 in common variable immunodeficiency (CVID) compared to non-CVID using a population-based database.

FEATURES OF DEVELOPMENT OF GENERALIZED PERIODONTITIS IN PERSONS WITH SECRETORY IMMUNOGLOBULIN A DEFICIENCY AND ITS TREATMENT (LITERATURE REVIEW)

The aim: To present data on the possibility of occurrence and active progression of generalized periodontitis in persons with secretory immunoglobulin A deficiency and possible methods of its correction. Мaterials and methods: Analytical elaboration of scientific and medical literature based on the immunological aspect of generalized periodontitis. Conclusions: The deficiency of secretory immunoglobulin A may occur in cases of primary or secondary insufficiency of the immune system. Selective IgA deficiency is an example of primary insufficiency of the immune system. Secondary immunodeficiency disorders is a clinical and immunological syndrome that develops against the background of a previously normally functioning immune system, characterized by a steady decrease in quantitative or functional indicators of specific or(and) nonspecific factors of immunoresistance. Insufficient awareness of dentists about certain aspects of the etiology and pathogenesis of generalized periodontitis leads to deterioration of treatment results.

Efficacy of Subcutaneous Immunoglobulin Replacement Therapy in Treating Secondary Immunodeficiency Disorders

In 1952, the first immunoglobulin products, made from human plasma, were used to combat infectious diseases such as primary immunodeficiencies during World War II. In addition, during the last 50 years, further research has been conducted to prove whether or not immunoglobulin therapy can truly be effective against primary immunodeficiencies such as X-linked agammaglobulinemia or Common Variable Immunodeficiency Disorder through both intravenous and subcutaneous administration. Intravenous administration has been effective in increasing overall Ig serum concentration in the blood for patients with primary or secondary disorders. However, as more research was conducted, scientists had concluded that the overall cost, maintenance, and at times, lack of efficiency, makes intravenous administration a burden. Thus, scientists have looked for an alternative through subcutaneous administration. For patients with primary immunodeficiencies, subcutaneous has been proven effective in increasing immunoglobulin concentration, even more than intravenous has. The benefit of subcutaneous administration at-home, the low cost, and the heightened efficacy make subcutaneous administration far better than intravenous for primary immunodeficiency patients. However for secondary immunodeficiency patients, the efficacy of subcutaneous administration has not been fully proven and the research is scarce and unreliable. Our literary review explores the advent of immunoglobulin therapy and its past research on both intravenous and subcutaneous administration for primary and secondary immunodeficiency disorders. We sought out to find potential experimental values researchers can conduct experiments to enhance the research on subcutaneous administration for secondary immunodeficiency patients.

Achieving equitable management of allergic disorders and primary immunodeficiency in a Black, Asian and Minority Ethnic population

Achieving equitable management of allergic disorders and primary immunodeficiency in a Black, Asian and Minority Ethnic population

Bioengineered Immunotherapy Techniques for the Treatment of Select Secondary Immunodeficiency Disorders

The inner workings of the immune system are quite complex. Each component works diligently in order to protect us from invaders such as pathogens: viruses, microbes, and fungi. Unfortunately, the immune system may become dysfunctional, which can result in secondary immunodeficiency diseases. The treatments available for these disorders and diseases of the immune system do not typically serve to cure, and much too often the side effects associated can exacerbate the conditions. As an alternative, the area of immunotherapy seeks to remedy the limitations of today’s medicine. Through this review, insight into the current conventional treatments available for select secondary immunodeficiency diseases will be provided, particularly in Human Immunodeficiency Virus disease and Systemic Lupus Erythematosus. The modern immunotherapy approaches that are underway will then be analyzed in their capacity and potential to treat these defects of the immune system.

Combined Treatment with Zinc Aspartate and Intravenous Immunoglobulins (IVIGs) Ameliorates Experimental Autoimmune Encephalomyelitis (EAE).

Intravenous immunoglobulins (IVIGs) are widely used in replacement therapy of primary and secondary immunodeficiency disorders and in approved autoimmune indications. In addition, IVIG application is used off-label for treatment of other autoimmune diseases, e.g., multiple sclerosis (MS), an inflammatory autoimmune disorder with a clear T cell-mediated immune pathogenesis. The trace element zinc is shown to play a regulatory role in the maintenance of immune functions. Changes of zinc homeostasis affect both the innate and the adaptive immune system. On one hand, therapeutic zinc supplementation can normalize impaired immune functions due to zinc deficiency. On the other hand, therapeutic zinc supplementation is under consideration as a possible option to treat T cell-mediated autoimmune diseases. The aim of the present study was to investigate the influence of IVIG (Octagam®), zinc aspartate (Unizink®), and the combined application of both preparations in the experimental autoimmune encephalomyelitis (EAE), the animal model of MS. Therapeutic intraperitoneal application of zinc aspartate significantly diminished clinical signs during the relapsing-remitting phase of EAE in SJL/J mice. In contrast, IVIG given in a therapeutic manner did not influence the course of EAE. Interestingly, the combined application of both, IVIG and zinc aspartate, significantly reduced the severity of the disease during the acute and the relapsing-remitting phase of the EAE. Our data suggest that the combination of IVIG and zinc aspartate may have beneficial effects in autoimmune diseases, like MS. Further studies should verify the benefit of a controlled immunosuppressive therapy with IVIG and zinc for such diseases.

Epstein-Barr Virus+ Smooth Muscle Tumors as Manifestation of Primary Immunodeficiency Disorders.

Epstein–Barr virus positive (EBV+) smooth muscle tumors (SMTs) constitute a very rare oncological entity. They usually develop in the context of secondary immunodeficiency caused by human immunodeficiency virus infection or immunosuppressive treatment after solid organ transplantation. However, in a small fraction of predominantly pediatric patients, EBV+ SMTs may occur in patients with primary immunodeficiency disorders (PIDs), such as GATA2 and CARMIL2 deficiency. In secondary immunodeficiencies and when the underlying condition can not be cured, the treatment of EBV+ SMTs is based on surgery in combination with antiretroviral and reduced or altered immunosuppressive pharmacotherapy, respectively. Importantly, without definitive reconstitution of cellular immunity, long-term survival is poor. This is particularly relevant for patients with EBV+ SMTs on the basis of PIDs. Recently, allogeneic hematopoietic stem cell transplantation resulted in cure of immunodeficiency and EBV+ SMTs in a GATA2-deficient patient. We propose that in the absence of secondary immunodeficiency disorders patients presenting with EBV+ SMTs should be thoroughly evaluated for PIDs. Allogeneic hematopoietic stem cell transplantation should be taken into consideration, ideally in the setting of a prospective clinical trial.

Clinical experiences in primary and secondary immunodeficiencies and immune-mediated conditions using Gammanorm(®).

Treatment for primary and secondary immunodeficiency disorders focuses on prevention and management of infections, using immunoglobulin G (IgG) replacement therapy with regular intravenous or subcutaneous IgG (SCIG) infusions. SCIG therapy has many advantages including improved efficacy and tolerability, enhanced patient satisfaction and lower costs. A number of SCIG preparations are available, including Gammanorm(®) (Octapharma AG), a ready-to-use 16.5% liquid preparation of IgG, with low viscosity, well suited to self-administration and a long history of use. Clinical experience with Gammanorm has shown that it is effective and well tolerated in children and adults, including pregnant women, for primary and secondary immunodeficiency disorders. Recent data also suggest SCIG may have a role in the treatment of certain immune-mediated conditions.

7th International Immunoglobulin Conference: Immunodeficiencies.

Most primary immunodeficiency disorders (PID) are the result of single gene defects. Based on this fact, more than 240 different entities have been identified. Those PIDs with predominant antibody deficiency are treated with immunoglobulin (Ig) replacement therapy. This review focuses on the diagnosis, clinical characteristics and treatment of patients suffering from PID, or secondary immunodeficiency disorders (SID) caused, for instance, by irradiation, immunosuppressive drugs or thymectomy. Common variable immunodeficiency (CVID) is the most commonly diagnosed and least understood form of PID, with a heterogeneous range of symptoms and genotypes, requiring individualized treatment plans. This includes adjusting the dose and treatment interval, administrating Ig by intravenous or subcutaneous injection by either pump or push, and finally deciding which treatment options are best for a given patient. Ig therapy can also be used to treat immunodeficiencies resulting from lymphoproliferative and autoimmune diseases or immunosuppression following organ transplantation; however, there is an urgent need for research in this field. Accurate and early diagnosis of PID is important to ensure that optimal treatment is started early to maintain the patient's health. Detailed patient registries have been established to increase awareness of PID, as well as provide a valuable resource for further research.

Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy and other primary immunodeficiency diseases help to resolve the nature of protective immunity against chronic mucocutaneous candidiasis

This review summarizes and discusses the most recent and important publications describing Mendelian diseases associated with susceptibility to chronic mucocutaneous candidiasis (CMC) as a means of gaining insight into the pathogenesis of this immunodeficiency. Impairment to T helper 17 (Th17) cell-associated signalling pathways are common in immunodeficiency syndromes associated with CMC infections. Mutations in CARD9, STAT3, IL17RA, IL17F, STAT1, and IL12RB and polymorphisms in Dectin 1 and interleukin-22 (IL-22) encoding genes have been shown to impair the development or function of Th17 cells and are associated with susceptibility to candidiasis. Studies on autoimmune polyendocrinopathy candidiasis ectodermal dystrophy have revealed autoimmunity to Th17 cytokines and cells as the basis for CMC. IL-17A, IL-17F, and IL-22 induce production of antimicrobial peptides and chemoattractants that recruit neutrophils in response to invading fungi. Th17 cell-associated cytokines may play a role in shaping the host's microbiome (that competes with C. albicans) preventing overgrowth of this pathogen. Recent evidence also suggests that IL-22 together with IL-17F might be the most important Th17 cytokine in protection against Candida. Dissection of critical molecular and immunological mechanisms will allow the development of new treatments for primary and secondary immunodeficiency disorders resulting in chronic Candida infections.

Management of secondary immune deficiencies

Management of secondary immune deficiencies

Selective antibody deficiency and its relation to the IgG2 and IgG3 subclass titers in recurrent respiratory infections.

Selective antibody deficiency with normal immunoglobulins (SADNI) may be identified as part of distinct primary or secondary immunodeficiency disorders. The clinical manifestations include recurrent, often severe or prolonged, upper or lower respiratory tract infections. To evaluate SADNI in patients with recurrent sinopulmonary infections and its relation to IgG subclass deficiencies. In a case-control study, anti-pneumococcal antibody titer and IgG2, IgG3 levels before injection of pneumococcal vaccine and anti-pneumococcal antibody titer at least 4 weeks after vaccination were measured in 46 patients and 54 controls. The results were compared using student's t-test. There was a significant correlation between age and anti-pneumococcal antibody titers before and after vaccination in patients. No significant relation was found between pre and post vaccination pneumococcal antibody titer and IgG2 and IgG3 in cases and controls (p>0.05). The mean of anti-pneumococcal antibody before and after vaccination were significantly different in cases and controls and were higher in control group (p=0.01, p=0.001, respectively). Anti-pneumococcal antibody titers in 97.8% of cases and 100% of controls group were normal (>3.4 µg/ml). 34.8% of cases and 9.1% of controls had low titers of anti-pneumococcal antibody (<20 µg/ml) while 18.7% of cases and no controls failed to respond to vaccine. Evaluation of anti-pneumococcal antibody titer in patients with recurrent, chronic and severe respiratory infections with normal immunoglobulin levels seems to be necessary as early diagnosis. Treatment of such cases could prevent later sequelae such as mastoiditis and bronchiecstasia.

The medical effects of mold exposure

Exposure to molds can cause human disease through several well-defined mechanisms. In addition, many new mold-related illnesses have been hypothesized in recent years that remain largely or completely unproved. Concerns about mold exposure and its effects are so common that all health care providers, particularly allergists and immunologists, are frequently faced with issues regarding these real and asserted mold-related illnesses. The purpose of this position paper is to provide a state-of-the-art review of the role that molds are known to play in human disease, including asthma, allergic rhinitis, allergic bronchopulmonary aspergillosis, sinusitis, and hypersensitivity pneumonitis. In addition, other purported mold-related illnesses and the data that currently exist to support them are carefully reviewed, as are the currently available approaches for the evaluation of both patients and the environment.

Itraconazole antagonizes store-operated influx of calcium into chemoattractant-activated human neutrophils.

We have investigated the effects of itraconazole (0.1-10 micro m), an antimycotic which is often used prophylactically in primary and secondary immunodeficiency disorders, including chronic granulomatous disease, on mobilization of Ca(2+) and restoration of Ca(2+) homeostasis following activation of neutrophils with FMLP or PAF. Transmembrane fluxes of Ca(2+), as well as cytosolic concentrations of the cation were measured using a combination of spectrofluorimetric and radiometric procedures. The abruptly occurring increases in cytosolic Ca(2+) following activation of the cells with either FMLP (1 micro m) or PAF (200 nm) were unaffected by itraconazole. However, the subsequent store-operated influx of the cation was attenuated by itraconazole at concentrations of 0.25 micro m and higher. The itraconazole-mediated inhibition of uptake of Ca(2+) was not associated with detectable alterations in the intracellular concentrations of cyclic AMP, ATP or inositol triphosphate, and appeared to be compatible with antagonism of store-operated Ca(2+) channels. Although a secondary property, this anti-inflammatory activity of itraconazole, if operative in vivo, may be beneficial in conditions associated with dysregulation of neutrophil Ca(2+) handling such as CGD.

Immunodeficiency disorders.

Hematological complications occur frequently in patients with both primary and secondary immunodeficiency disorders. Anemia, thrombocytopenia or leukopenias may bring these individuals to the attention of hematologists. Conversely, evidence suggesting a lymphoproliferative disorder may be the cause for referral. This session will provide an update on the diagnosis and treatment of immunodeficiency diseases ranging from isolated defects in antibody production to the severe combined immunodeficiencies (SCID). Immunodeficiency diseases have traditionally been defined as defects in the development and function of T and B cells, the primary effector cells of specific cellular and humoral immunity. However, it has become increasingly evident that innate immune mechanisms contribute greatly to host defense, either through acting alone or by enhancing specific T and B cell responses. In Section I, Dr. Lewis Lanier reviews the burgeoning information on the extensive families of activating and inhibitory immunoreceptors that are expressed on NK cells, dendritic cells, T and B cells, and phagocytic cells. He provides an overview on the biological functions of these receptors in host defense. In Section II, Dr. Mary Ellen Conley defines the spectrum of antibody deficiency disorders, the most frequently occurring types of primary immunodeficiencies. She covers the different defects in B-cell development and function that lead to antibody deficiencies, and includes diagnosis and therapy of these disorders. In Section III, Dr. Jennifer Puck discusses the diagnosis and treatment of the different types of SCID. She describes the genetic basis for SCID, and the benefits, pitfalls, and complications of gene therapy and bone marrow transplantation in SCID patients.