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J Clin Immunol. 2024 Nov 16;45(1):43. doi: 10.1007/s10875-024-01832-4.

NO ABSTRACT

PMID:39547966 | DOI:10.1007/s10875-024-01832-4

BMC Infect Dis. 2024 Nov 14;24(1):1296. doi: 10.1186/s12879-024-09776-1.

ABSTRACT

BACKGROUND: Routine childhood immunization against varicella-zoster virus has led to a dramatic reduction in the incidence of primary varicella. However, there are rare, yet significant cases reported of reactivated Oka-strain varicella, primarily in immunocompromised hosts.

CASE PRESENTATION: A 16-year-old female with Hodgkin’s lymphoma developed a vesicular rash shortly after completing all chemotherapy treatment. Swabs obtained from the vesicles were positive for varicella-zoster virus. By the time of hospitalization, the patient developed a disseminated rash involving multiple dermatomes. Subsequent polymerase chain reaction confirmed Oka vaccine-strain varicella-zoster virus. The patient had previously received a primary series of immunizations against varicella in 2008 and 2012, with her 2nd dose given 11 years prior to her development of vaccine-strain herpes zoster and 10 years prior to her diagnosis of Hodgkin’s lymphoma, respectively. The patient was treated with parenteral acyclovir upon hospitalization and monitored clinically for cutaneous disease progression as well as sequelae. After 8 days of inpatient treatment, her rash had stopped spreading with no new lesions. All earlier lesions had crusted over. No serious sequelae of disease such as pneumonitis, hepatitis, encephalitis, or meningitis occurred, and she made a complete recovery.

CONCLUSIONS: There are individual and community-wide benefits to childhood immunization against varicella. This case highlights an unusual presentation of disseminated vaccine-strain herpes zoster in an adolescent with secondary immunodeficiency 11 years after completing primary immunization. In addition, this case informs pediatricians of complications that can arise in immunized subjects if they become immunosuppressed years later. The only way to distinguish between wild-type and vaccine-strain herpes zoster was by viral genotyping. Providers should be cognizant of potential vaccine virus reactivation in their differential. Considerations for work-up and management should include infection control and viral resistance in refractory cases.

PMID:39543470 | DOI:10.1186/s12879-024-09776-1

J Clin Immunol. 2024 Nov 14;45(1):41. doi: 10.1007/s10875-024-01841-3.

NO ABSTRACT

PMID:39540960 | DOI:10.1007/s10875-024-01841-3

Immunogenetics. 2024 Nov 14;77(1):2. doi: 10.1007/s00251-024-01359-3.

ABSTRACT

Genetic variants in Folliculin interacting protein 1 (FNIP1) were recently discovered as monogenic causes for immunodeficiency and cardiomyopathy, with only a few patients diagnosed thus far. In this study, we describe a patient harboring a novel genetic variant in FNIP1 causing immunodeficiency with cardiac involvement. Clinical and immunological workups were performed. Genetic evaluation utilizing whole-exome sequencing (WES) and Sanger sequencing was conducted. The index patient (subject II-4) presented with hypertrophic cardiomyopathy, recurrent infections, and chronic diarrhea during infancy. Immune workup revealed agammaglobulinemia and a lack of B lymphocytes. Genetic evaluation identified a homozygous 13-bp duplication variant in FNIP1 (c.52_64dupGCGCCCGGCCGCG, p. Asp22GlyfsTer21) resulting in a frameshift in exon 1/18. She was treated with supplemental intravenous immunoglobulins (IVIg) with good control of sinopulmonary and gastrointestinal manifestations. Her sibling (subject II-1) had similar clinical features, along with dysmorphic facial features and hypotony, and succumbed to cardiogenic shock at the age of 2 months, prior to genetic evaluation. Diagnosis of novel immunodeficiencies promotes our understanding of the immune system, enabling genetic counseling as herein, and may assist in the development of novel medical therapies in the future. FNIP1 loss-of-function should be considered in patients presenting in infancy with cardiac manifestations along with agammaglobulinemia (and B-cell lymphopenia).

PMID:39537849 | DOI:10.1007/s00251-024-01359-3

Int J Rheum Dis. 2024 Nov;27(11):e15405. doi: 10.1111/1756-185X.15405.

ABSTRACT

AIM: To test the efficaciousness of the 10 warning signs of Jeffrey Modell Foundation (JMF) and routine laboratory tests in predicting Primary Immunodeficiencies (PIDs).

METHODS: Hospitalized children <12 years age satisfying at least two of 10 warning signs were subjected to routine and confirmatory tests.

RESULTS: Of 35 204 admitted patients, 66 satisfied the JMF criteria and 34 had PID. Also, 59% were infants, with a female preponderance. The most common immunodeficiency disorder group were antibody deficiencies and phagocyte defects (35.3%). Chronic granulomatous disease (CGD) was the commonest overall (29.4%). The need for intravenous antibiotics was the most sensitive (91%) criterion for predicting PID. When combined with positive family history of PID, sensitivity (94%) increased further. The two most specific indicators were recurrent ear infections (88%), and family history of PID (88%). The best positive predictor was family history of PID (69%), and the best negative predictor was recurrent sinus infections (58%). Significant association was found between persistent oral thrush and PID (p .043), and insufficient weight gain and antibody deficiencies (p .037). Absolute neutrophil count, CRP, and elevated ESR were also significantly associated with PIDs (p-values being .036, .011, and .014 respectively).

CONCLUSION: Out of all 10 JMF criteria, the three most important ones to predict PID were need for IV antibiotics, family history of PID, and recurrent ear infections.

PMID:39530581 | DOI:10.1111/1756-185X.15405

FASEB J. 2024 Nov 15;38(21):e70162. doi: 10.1096/fj.202401763R.

ABSTRACT

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 and PKD2, encoding polycystin-1 (PC1) and polycystin-2 (PC2), which are required for the regulation of the renal tubular diameter. Loss of polycystin function results in cyst formation. Atypical forms of ADPKD are caused by mutations in genes encoding endoplasmic reticulum (ER)-resident proteins through mechanisms that are not well understood. Here, we investigate the function of DNAJB11, an ER co-chaperone associated with atypical ADPKD. We generated mouse models with constitutive and conditional Dnajb11 inactivation and Dnajb11-deficient renal epithelial cells to investigate the mechanism underlying autosomal dominant inheritance, the specific cell types driving cyst formation, and molecular mechanisms underlying DNAJB11-dependent polycystic kidney disease. We show that biallelic loss of Dnajb11 causes cystic kidney disease and fibrosis, mirroring human disease characteristics. In contrast to classical ADPKD, cysts predominantly originate from proximal tubules. Cyst formation begins in utero and the timing of Dnajb11 inactivation strongly influences disease severity. Furthermore, we identify impaired PC1 cleavage as a potential mechanism underlying DNAJB11-dependent cyst formation. Proteomic analysis of Dnajb11- and Pkd1-deficient cells reveals common and distinct pathways and dysregulated proteins, providing a foundation to better understand phenotypic differences between different forms of ADPKD.

PMID:39530576 | DOI:10.1096/fj.202401763R

Eur Ann Allergy Clin Immunol. 2024 Nov 11. doi: 10.23822/EurAnnACI.1764-1489.373. Online ahead of print.

ABSTRACT

Background.Omega-3 fatty acids are involved in many processes in the human body. Their beneficial effects were documented mainly in relation to cardiovascular and immune systems. Patients with immunodeficiencies with predominantly antibody defects due to their reduced immunoglobulin levels should have factors adversely affecting the course of the disease eliminated. Methods. Nineteen primary immunodeficient patients with predominant antibody defects (out of which fourteen with CVID) and eighteen immunocompetent participants had their blood tested in order to determine the concentration of EPA, DHA and omega-3 index values. The Mann-Whitney U tests were used to determine statistical significance. Results. Immunodeficient participants, especially with CVID, overall tend to have a slightly lower mean concentration of omega-3 fatty acids such as DHA and in particular EPA (CVID: 0.86% ± 0.28% vs 1.06% ± 0.31%, p = 0.095) as compared with the control group and the differences were most evident among patients aged 30-39 (0.67 ± 0.16% vs 1.12 ± 0.12%, p = 0.025). 63% of patients with immunodeficiency had an omega-3 index value between 4-8, compared to 39% in the control group. 37% of participants with predominantly antibody defects had an omega-3 index value > 8% (29% of all CVID group) compared with 61% of the control group. None of the participants achieved a result of 4% or lower. People without immunodeficiency consumed products rich in omega-3 acids more often. Conclusions. These findings suggest that primary immunodeficient patients with predominantly antibody defects tend to have lower omega-3 index values, albeit not significantly and seem to have higher cardiovascular risk than the control group. Research has also shown that education is needed regarding the effects and necessity of consuming products rich in omega-3 fatty acids, especially in patients with immunodeficiency.

PMID:39530141 | DOI:10.23822/EurAnnACI.1764-1489.373

Inflammation. 2024 Nov 12. doi: 10.1007/s10753-024-02183-3. Online ahead of print.

ABSTRACT

Patients with non-infectious systemic inflammation may suffer from one of many diseases, including hyperinflammation (HI), autoinflammatory disorders (AID), and systemic autoimmune disease (AI). Despite their clinical overlap, the pathophysiology and patient management differ between these disorders. We aimed to investigate blood biomarkers able to discriminate between patient groups. We included 44 patients with active clinical and/or genetic systemic inflammatory disease (9 HI, 27 AID, 8 systemic AI) and 16 healthy controls. We quantified 55 serum proteins and combined multiple machine learning algorithms to identify five proteins (CCL26, CXCL10, ICAM-1, IL-27, and SAA) that maximally separated patient groups. High ICAM-1 was associated with HI. AID was characterized by an increase in SAA and decrease in CXCL10 levels. A trend for higher CXCL10 and statistically lower SAA was observed in patients with systemic AI. Principal component analysis and unsupervised hierarchical clustering confirmed separation of disease groups. Logistic regression modelling revealed a high statistical significance for HI (P = 0.001), AID, and systemic AI (P < 0.0001). Predictive accuracy was excellent for systemic AI (AUC 0.94) and AID (0.91) and good for HI (0.81). Further research is needed to validate findings in a larger prospective cohort. Results will contribute to a better understanding of the pathophysiology of systemic inflammatory disorders and can improve diagnosis and patient management.

PMID:39528768 | DOI:10.1007/s10753-024-02183-3

Allergy Asthma Proc. 2024 Nov 1;45(6):434-437. doi: 10.2500/aap.2024.45.240071.

ABSTRACT

Background: Hereditary angioedema (HAE) is a complex disorder with a wide array of treatment options. Shared decision-making (SDM) should be used to ensure that patients are choosing their best treatment option. The goal was to develop and psychometrically test a brief instrument for assessing the patient’s perspective of the SDM process during his or her clinical encounters with an HAE specialist/allergist. Method: We hypothesized that SDM could be used effectively to help patients in their choice of therapy for HAE. Ten HAE treating physicians from the United States with a total of 50 patients with HAE used SDM to help patients choose the best prophylactic therapies (oral kallikrein inhibitor, androgens, subcutaneous C1 inhibitor replacement therapy, intravenous C1 inhibitor replacement therapy, monoclonal antibody kallikrein inhibitor) for their HAE and then completed surveys to analyze the effectiveness of the implementation of SDM as a quality indicator in health services assessment. Results: The congruence of answers between the physicians and the patients was then analyzed; 90% of the patient-physician pairs agreed that the advantages and disadvantages of the treatment options were precisely explained; 92% of the patient-physician pairs agreed that the physician helped them understand all the information and that the physician asked them which treatment option they preferred; 88% of the pairs agreed that the different treatment options were thoroughly weighed and 92% of the pairs felt that they selected a treatment option together. Conclusion: In summary, SDM is being implemented by treating physicians to determine the best management options for their patients with HAE.

PMID:39517078 | DOI:10.2500/aap.2024.45.240071

Ocul Immunol Inflamm. 2024 Nov 13:1-9. doi: 10.1080/09273948.2024.2423870. Online ahead of print.

ABSTRACT

PURPOSE: The survey aims to explore the use of existing nomenclature and current clinical and multimodal imaging (MMI) approach in diagnosing white dot syndromes (WDS) among uveitis and retina specialists.

METHODS: The members of the International Uveitis Study Group (IUSG) task force MUV (Multimodal imaging in UVeitis) developed a survey. The questionnaire, created using Qualtrics, consisted of 22 questions. The responses were compared against regions, workplace setting, sub-specialty, and experience of the participants.

RESULTS: A total of 432 participants initiated the background section; 343 initiated the investigation section and 263/343 completed the survey (76.7%). The majority (43.7%) reported a specialty/practice focus mostly on uveitis, 32.2% on uveitis and retina, and 20.1% mostly on retina. Specifically, 55.7% were in practice > 10 years post-fellowship and 65.8% worked in academic settings. The term WDS was not universally used in clinical practice, with no significant differences by region, subspecialty, experience, workplace setting or number of WDS patients managed in the prior year (p > 0.01). Nearly 90% of participants reported using MMI to diagnose WDS. More than 70% advocated redefining the nomenclature and classification of WDS based on the primary anatomical location of disease using MMI without significant regional or professional differences (p > 0.01).

CONCLUSION: These results underscore the widespread adoption of MMI among uveitis and retina specialists in the characterization of entities traditionally grouped under the term WDS. Respondents strongly agree that MMI provides a precise distinction between these posterior uveitis, advocating for the overcoming of the clinical term WDS in favor of a patho-anatomic redefinition.

PMID:39535406 | DOI:10.1080/09273948.2024.2423870