Patients with primary immunodeficiencies are a reservoir of poliovirus and a risk to polio eradication

ABSTARCT: Immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) have been isolated from primary immunodeficiency (PID) patients exposed to oral poliovirus vaccine (OPV). Patients may excrete poliovirus strains for months or years; the excreted viruses are frequently highly divergent from the parental OPV and have been shown to be as neurovirulent as wild virus. Thus, these patients represent a potential reservoir for transmission of neurovirulent polioviruses in the post-eradication era. In support of WHO recommendations to better estimate the prevalence of poliovirus excreters among PIDs and characterize genetic evolution of these strains, 635 patients including 570 with primary antibody deficiencies and 65 combined immunodeficiencies were studied from 13 OPV-using countries. Two stool samples were collected over 4 days, tested for enterovirus, and the poliovirus positive samples were sequenced. Thirteen patients (2%) excreted polioviruses, most for less than 2 months following identification of infection. Five (0.8%) were classified as iVDPVs (only in combined immunodeficiencies and mostly poliovirus serotype 2). Non-polio enteroviruses were detected in 30 patients (4.7%). Patients with combined immunodeficiencies had increased risk of delayed poliovirus clearance compared to primary antibody deficiencies. Usually, iVDPV was detected in subjects with combined immunodeficiencies in a short period of time after OPV exposure, most for less than 6 months. Surveillance for poliovirus excretion among PID patients should be reinforced until polio eradication is certified and the use of OPV is stopped. Survival rates among PID patients are improving in lower and middle income countries, and iVDPV excreters are identified more frequently. Antivirals or enhanced immunotherapies presently in development represent the only potential means to manage the treatment of prolonged excreters and the risk they present to the polio endgame. Keywords: Poliovirus eradication, Immunodeficiency-associated vaccine-derived polioviruses, Oral poliovirus vaccine, Humoral immunodeficiency, Combined immunodeficiency, Primary immunodeficienc

Long-term outcome of LRBA deficiency in 76 patients after various treatment modalities as evaluated by the immune deficiency and dysregulation activity (IDDA) score

Background: Recent findings strongly support hematopoietic stem cell transplantation (HSCT) in patients with severe presentation of LPS-responsive beige-like anchor protein (LRBA) deficiency, but long-term follow-up and survival data beyond previous patient reports or meta-reviews are scarce for those patients who do not receive a transplant.Objective: This international retrospective study was conducted to elucidate the longitudinal clinical course of patients with LRBA deficiency who do and do not receive a transplant.Method: We assessed disease burden and treatment responses with a specially developed immune deficiency and dysregulation activity score, reflecting the sum and severity of organ involvement and infections, days of hospitalization, supportive care requirements, and performance indices.Results: Of 76 patients with LRBA deficiency from 29 centers (median follow-up, 10 years; range, 1-52), 24 underwent HSCT from 2005 to 2019. The overall survival rate after HSCT (median follow-up, 20 months) was 70.8% (17 of 24 patients); all deaths were due to nonspecific, early, transplant-related mortality. Currently, 82.7% of patients who did not receive a transplant (43 of 52; age range, 3-69 years) are alive. Of 17 HSCT survivors, 7 are in complete remission and 5 are in good partial remission without treatment (together, 12 of 17 [70.6%]). In contrast, only 5 of 43 patients who did not receive a transplant (11.6%) are without immunosuppression. Immune deficiency and dysregulation activity scores were significantly lower in patients who survived HSCT than in those receiving conventional treatment (P = .005) or in patients who received abatacept or sirolimus as compared with other therapies, and in patients with residual LRBA expression. Higher disease burden, longer duration before HSCT, and lung involvement were associated with poor outcome.Conclusion: The lifelong disease activity, implying a need for immunosuppression and risk of malignancy, must be weighed against the risks of HSCT.Transplantation and immunomodulatio

Restless legs syndrome in childhood: A case report [Çocukluk çaginda huzursuz bacak sendromu: Bir vaka takdimi]

Restless legs syndrome is a neurological movement disorder characterized by a distressing desire to move legs or sometimes other extremities, associated with a marked sense of discomfort usually in the leg or other affected body part. It follows a circadian pattern and the symptoms worsen at rest, in the evening or at night and there is at least momentary relief by activity. Genetic and environmental factors cause the restless legs syndrome. Recent researches have achieved the definition of the pathophysiologic mechanisms of the disorder. It is suggested that iron deficiency is a primary factor in the development of the symptoms. Because the symptoms become much worse at night while sleeping, it causes sleep disturbance and so it may severely disrupt normal life functioning. Although it is more common in adult life, it may occur more frequently in children than previously recognized. This syndrome is a clinical diagnosis that relies entirely on the patient's symptoms, thus the interviews should involve a general medical history about the associated features. Especially in the children experiencing sleep disturbance or growing pain, restless legs syndrome must also be considered in the differential diagnosis

Early-onset inflammatory bowel disease

[No abstract available

Does intravenous immunoglobulin therapy prolong immunodeficiency in transient hypogammaglobulinemia of infancy?

Transient hypogammaglobulinemia of infancy (THI) is characterized by recurrent infections and one or more reduced serum immunoglobulin levels. Typically, THI patients recover spontaneously, mostly within 30-40 months of age, but sometimes recovery may be delayed until 5-6 years of age. The use of intravenous immunoglobulin (IVIg) as an alternative to antibiotic prophylaxis remains contraversial also in symptomatic THI patients. In fact, some authors believe that IVIg therapy may cause a delay in the maturation of the humoral immune system because of the interference from passively transfered antibodies. The aim of this study was to investigate the effect of IVIg replacement on recovery from immunodeficiency in THI patients and determine new parameters in order to include these patients in IVIg therapy groups. In this retrospective study, 43 patients (65%) received IVIg replacement therapy while 23 patients (34.8%) showed spontaneous normalization without IVIg. The percentages of patients who had more than six times the number of febrile infections in a year decreased from 91% to 21% in the group receiving IVIg treatment. At admission, before being recruited to IVIg therapy, serum immunoglobulin G (IgG) levels and antihemophilus B (Hib) antibody titers were found to be significantly low in cases who were selected for IVIg replacement. The percentages of patients who did not have protective levels of anti-Hib, anti-rubella or anti-rubeola-IgG were also significantly high in IVIg cases. There was no statistically significant difference in the age at which IgG levels normalized between the IVIg and the non-IVIg group. Patients in the IVIg group and non-IVIg group reached normal IgG levels at the age of 42.9±22.0 and 40.7±19.8 months, respectively. In conclusion, IVIg infusions do not cause a delay in the maturation of the immune system in THI patients. Besides the well-established criteria, very low and non-protective specific antibody responses against previously applied vaccines are important factors to consider when selecting patients for IVIg therapy. © F. Tocchioni et al., 2013

Fc? receptor polymorphisms in patients with transient hypogammaglobulinemia of infancy presenting with mild and severe infections

PubMed ID: 26708396Background: Patients with transient hypogammaglobulinaemia of infancy (THI) may have mild infections or be asymptomatic. About 20% of THI patients have very severe and recurrent infections and receive intravenous immunoglobulins (IVIg) for replacement therapy and infection prophylaxis. It is still not clear why some THI patients are severely symptomatic; it has been suggested that there might be additional immunologic or environmental factors or other co-morbidities. Objective: As an immunological factor, Fc? receptor polymorphisms (H/H-131, H/R-131 and R/R-131 for Fc?IIa; V/V-158, V/F-158 and F/F- 158 for Fc?RIIIa; NA1/NA1, NA1/NA2 and NA2/NA2 for Fc?RIIIb) were analysed in THI patients who had very severe infections and need hospitalisation (treated with IVIg) (n:18) and in THI patients who were asymptomatic or had mild infections (treated with antibiotics or received no medication) (n:25). Results: Genotypic distributions between two groups did not deviate significantly from the Hardy-Weinberg equilibrium expectations (p > 0.05) and odds ratios for “disease risk estimate” did not show any dominance for any genotype. Allele frequencies did not show any significant difference between the two groups (p >0.05). The number of infections per year for each Fc? receptor genotype was not significantly different between both groups. Conclusion: There is no association between the heterogeneous clinical picture of THI patients and Fc? receptor gene polymorphisms. © 2009 is a Digital Portal of health science journals in Thailand