Manish Butte

Inflammopharmacology. 2023 May 17. doi: 10.1007/s10787-023-01222-z. Online ahead of print.

ABSTRACT

Sjögren’s syndrome (SS) is characterised as keratoconjunctivitis sicca (dry eyes), xerostomia (dry mouth) commonly associated with salivary gland enlargement, and is referred to as Primary Sjögren’s syndrome. It is known as Secondary Sjögren’s syndrome when it occurs in patients, with connective tissue disease, such as rheumatoid arthritis, systemic lupus erythematosus, polyarthritis nodosa, polymyositis, and systemic sclerosis. SS has also been associated with chronic graft-versus-host disease after allogeneic bone marrow transplantation, human immunodeficiency syndrome (AIDS), hepatitis C infection (HCV), chronic biliary cirrhosis, neoplastic and myeloplastic syndromes, fibromyalgia, and chronic fatigue syndrome.

PMID:37195497 | DOI:10.1007/s10787-023-01222-z

Clin Case Rep. 2023 May 12;11(5):e7341. doi: 10.1002/ccr3.7341. eCollection 2023 May.

ABSTRACT

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder that is characterized by deficiencies in the phagocytes capacity to eliminate ingested microorganisms, which frequently causes bacterial and fungal infections. The extensive involvement of the lungs, ribs, and vertebrae that is complicated by multiple abscesses from aspergillosis is rare. in this study, we report a 13-year-old boy with CGD who experienced concurrent pneumonia, rib osteomyelitis, spondylodiscitis, paravertebral, and epidural abscesses as a result of Aspergillus flavus infection with associated computed tomography scan and magnetic resonance imaging findings. Patients with CGD are susceptible to Aspergillus infection. Correct diagnosis based on clinical and paraclinical findings as well as choosing the best treatment regimen is essential for achieving a favorable outcome.

PMID:37192846 | PMC:PMC10182263 | DOI:10.1002/ccr3.7341

Biomedicines. 2023 Mar 28;11(4):1042. doi: 10.3390/biomedicines11041042.

ABSTRACT

Patients with antibody deficiency disorders, such as primary immunodeficiency (PID) or secondary immunodeficiency (SID) to B-cell lymphoproliferative disorder (B-CLPD), are two groups vulnerable to developing the severe or chronic form of coronavirus disease caused by SARS-CoV-2 (COVID-19). The data on adaptive immune responses against SARS-CoV-2 are well described in healthy donors, but still limited in patients with antibody deficiency of a different cause. Herein, we analyzed spike-specific IFN-γ and anti-spike IgG antibody responses at 3 to 6 months after exposure to SARS-CoV-2 derived from vaccination and/or infection in two cohorts of immunodeficient patients (PID vs. SID) compared to healthy controls (HCs). Pre-vaccine anti-SARS-CoV-2 cellular responses before vaccine administration were measured in 10 PID patients. Baseline cellular responses were detectable in 4 out of 10 PID patients who had COVID-19 prior to vaccination, perceiving an increase in cellular responses after two-dose vaccination (p < 0.001). Adequate specific cellular responses were observed in 18 out of 20 (90%) PID patients, in 14 out of 20 (70%) SID patients and in 74 out of 81 (96%) HCs after vaccination (and natural infection in some cases). Specific IFN-γ response was significantly higher in HC with respect to PID (1908.5 mUI/mL vs. 1694.1 mUI/mL; p = 0.005). Whereas all SID and HC patients mounted a specific humoral immune response, only 80% of PID patients showed positive anti-SARS-CoV-2 IgG. The titer of anti-SARS-CoV-2 IgG was significantly lower in SID compared with HC patients (p = 0.040), without significant differences between PID and HC patients (p = 0.123) and between PID and SID patients (p =0.683). High proportions of PID and SID patients showed adequate specific cellular responses to receptor binding domain (RBD) neoantigen, with a divergence between the two arms of the adaptive immune response in PID and SID patients. We also focused on the correlation of protection of positive SARS-CoV-2 cellular response to omicron exposure: 27 out of 81 (33.3%) HCs referred COVID-19 detected by PCR or antigen test, 24 with a mild course, 1 with moderate symptoms and the remaining 2 with bilateral pneumonia that were treated in an outpatient basis. Our results might support the relevance of these immunological studies to determine the correlation of protection with severe disease and for deciding the need for additional boosters on a personalized basis. Follow-up studies are required to evaluate the duration and variability in the immune response to COVID-19 vaccination or infection.

PMID:37189660 | DOI:10.3390/biomedicines11041042

Urol Case Rep. 2023 May 1;48:102409. doi: 10.1016/j.eucr.2023.102409. eCollection 2023 May.

ABSTRACT

Chronic Granulomatous Disease is a primary immunodeficiency syndrome caused by a phagocytic defect, characterized by recurrent, life-threatening bacterial and fungal infections and an excessive inflammatory response. We present the case of a boy with disease’s symptoms mainly from the genitourinary tract. We describe diagnostic difficulties and atypical cystoscopic images, which showed bright morphotic elements of unclear etiology moving in the vessels of the bladder mucosa. These lesions were retrospectively interpreted as clusters of white blood cells (granulomas). Due to the lack of description of a similar phenomenon in the literature, we would like to make the recorded endoscopic images available.

PMID:37187765 | PMC:PMC10176158 | DOI:10.1016/j.eucr.2023.102409

Clin Case Rep. 2023 May 9;11(5):e7282. doi: 10.1002/ccr3.7282. eCollection 2023 May.

ABSTRACT

KEY CLINICAL MESSAGE: HHV8- and EBV-negative primary effusion lymphoma is an extremely rare neoplasm involving body cavities without detectable tumor mass. It usually presents in elderly patients without known immunodeficiency. Compared to primary effusion lymphoma, it has a better prognosis.

Primary effusion lymphoma (PEL) is a rare non-Hodgkin lymphoma confined exclusively to body cavities without detectable tumor masses. The term PEL-like is an entity similar to PEL in clinical presentation but without relation to human herpesvirus 8 (HHV8). We report a case of HHV8- and EBV-negative primary effusion-based lymphoma.

PMID:37180332 | PMC:PMC10167618 | DOI:10.1002/ccr3.7282

Front Immunol. 2023 Apr 27;14:1146841. doi: 10.3389/fimmu.2023.1146841. eCollection 2023.

ABSTRACT

BACKGROUND: Humoral and cellular immune responses are known to be crucial for patients to recover from COVID-19 and to protect them against SARS-CoV-2 reinfection once infected or vaccinated.

OBJECTIVES: This study aimed to investigate humoral and T cell responses to SARS-CoV-2 vaccination in patients with autoimmune diseases after the second and third vaccine doses while on rituximab and their potential protective role against reinfection.

METHODS: Ten COVID-19-naïve patients were included. Three time points were used for monitoring cellular and humoral responses: pre-vaccine to exclude virus exposure (time point 1) and post-second and post-third vaccine (time points 2 and 3). Specific IgG antibodies were monitored by Luminex and T cells against SARS-CoV-2 spike-protein by ELISpot and CoVITEST. All episodes of symptomatic COVID-19 were recorded.

RESULTS: Nine patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis and one with an undifferentiated autoimmune disease were included. Nine patients received mRNA vaccines. The last rituximab infusion was administered for a mean (SD) of 15 (10) weeks before the first vaccine and six patients were CD19-B cell-depleted. After a mean (SD) of 19 (10) and 16 (2) days from the second and third vaccine dose, IgG anti-SARS-CoV-2 antibodies were detected in six (60%) and eight (80%) patients, respectively. All patients developed specific T cell responses by ELISpot and CoVITEST in time points 2 and 3. Previous B cell depletion correlated with anti-SARS-CoV-2 IgG levels. Nine (90%) patients developed mild COVID-19 after a median of 7 months of the third dose.

CONCLUSION: Rituximab in patients with autoimmune diseases reduces humoral responses but does not avoid the development of T cell responses to SARS-CoV-2 vaccination, which remain present after a booster dose. A steady cellular immunity appears to be protective against subsequent reinfections.

PMID:37180097 | PMC:PMC10174323 | DOI:10.3389/fimmu.2023.1146841

Sci Immunol. 2023 May 12;8(83):eadd3955. doi: 10.1126/sciimmunol.add3955. Epub 2023 May 12.

ABSTRACT

Dendritic cells (DCs) mature in an immunogenic or tolerogenic manner depending on the context in which an antigen is perceived, preserving the balance between immunity and tolerance. Whereas the pathways driving immunogenic maturation in response to infectious insults are well-characterized, the signals that drive tolerogenic maturation during homeostasis are still poorly understood. We found that the engulfment of apoptotic cells triggered homeostatic maturation of type 1 conventional DCs (cDC1s) within the spleen. This maturation process could be mimicked by engulfment of empty, nonadjuvanted lipid nanoparticles (LNPs), was marked by intracellular accumulation of cholesterol, and was highly specific to cDC1s. Engulfment of either apoptotic cells or cholesterol-rich LNPs led to the activation of the liver X receptor (LXR) pathway, which promotes the efflux of cellular cholesterol, and repressed genes associated with immunogenic maturation. In contrast, simultaneous engagement of TLR3 to mimic viral infection via administration of poly(I:C)-adjuvanted LNPs repressed the LXR pathway, thus delaying cellular cholesterol efflux and inducing genes that promote T cell-mediated immunity. These data demonstrate that conserved cellular cholesterol efflux pathways are differentially regulated in tolerogenic versus immunogenic cDC1s and suggest that administration of nonadjuvanted cholesterol-rich LNPs may be an approach for inducing tolerogenic DC maturation.

PMID:37172103 | DOI:10.1126/sciimmunol.add3955

Pediatr Infect Dis J. 2023 Apr 27. doi: 10.1097/INF.0000000000003957. Online ahead of print.

ABSTRACT

BACKGROUND: We aimed to determine the frequency of bacteremia, septic shock and bacterial meningitis in pediatric liver transplant recipients (pLTRs) in the outpatient setting and to identify clinical factors associated with bacteremia.

METHODS: Multicenter retrospective study of pLTRs evaluated in the emergency department or outpatient clinic between 2010 and 2018 for suspected infection, defined as fever ≥38 °C or a blood culture obtained. We excluded patients with nontransplant immunodeficiency, multiorgan transplants or intestinal failure. The primary outcome was bacteremia; secondary outcomes included fluid-refractory septic shock, bacterial meningitis and antibiotic resistance. The unit of analysis was the encounter.

RESULTS: A total of 151 children had 336 encounters for infection evaluation within 2 years of transplant. Of 307 (91.4%) encounters with blood cultures, 17 (5.5%) had bacteremia, with 10 (58.8%) occurring within 3 months of transplant. Fluid-refractory septic shock and bacterial meningitis occurred in 7 out of 307 (2.8%) and 0 out of 307 encounters, respectively. Factors associated with bacteremia included closer proximity to transplant (<3 months) [odds ratio (OR): 3.6; 95% confidence interval (CI): 1.3-9.8; P = 0.01], shorter duration of illness (OR: 4.3; 95% CI: 1.5-12.0; P < 0.01) and the presence of a central venous catheter (CVC) (OR: 12.7; 95% CI: 4.4-36.6; P < 0.01). However, 5 (29.4%) encounters with bacteremia had none of these factors. Among Gram-positive pathogens, 1 out of 7 (14.2%) isolates were resistant to vancomycin. Among Gram-negative pathogens, 3 out of 13 (23.1%) isolates were resistant to 3rd generation cephalosporins.

CONCLUSIONS: Bacteremia was an important cause of infection within 2 years of pLTR. Clinical factors increased the risk of bacteremia. Further, large sample studies should derive multivariable models to identify those at high and low risk of bacteremia to optimize antibiotic use.

PMID:37171971 | DOI:10.1097/INF.0000000000003957

J Clin Immunol. 2023 May 12. doi: 10.1007/s10875-023-01501-y. Online ahead of print.

ABSTRACT

PURPOSE: Immunoglobulin E deficiency (IgED) (defined as IgE < 2 IU/mL) is enriched in patients with primary antibody deficiency (PAD). We hypothesized that selective IgED (sIgED) is a more sensitive predictor of the development of PAD than declining IgG, as IgE production typically requires two class switch recombination (CSR) events in contrast to IgG. Thus, the inability of patients with sIgED to mount an appropriate antibody response to a T-cell independent antigen or evidence of aberrant induction of ɛ germ line (ɛGL) or IgE heavy chain (IgEHC) transcripts in vitro would support the concept that sIgED is a biomarker for emerging PAD.

METHODS: We compared pre- and post-polysaccharide vaccination titers in healthy patients with sIgED without a history of recurrent infections or autoimmunity (n = 20) and in healthy controls (HCs) (n = 17). Subsequently, we assessed in vitro induction of εGL and IgEHC transcripts in patients with sIgED and HC (n = 6) in response to IL-4 + CD40L stimulation.

RESULTS: Thirty percent of patients with sIgED did not have a robust vaccine response compared to 0% of HCs (p = 0.017). Individuals with sIgED with an abnormal vaccine response demonstrated persistent germline mRNA expression in their B-cells at day 5, with lower levels of IgEHC, compared to both HCs and sIgED participants with a normal vaccine response.

CONCLUSION: Patients with sIgED are more likely to have abnormal antibody responses to a T cell-independent antigen and may have dysregulated CSR machinery. Following individuals with sIgED longitudinally may be beneficial in the early identification of PAD.

PMID:37169968 | DOI:10.1007/s10875-023-01501-y

JPGN Rep. 2021 Nov 29;3(1):e135. doi: 10.1097/PG9.0000000000000135. eCollection 2022 Feb.

ABSTRACT

Both severe combined immunodeficiency (SCID) syndrome and Duchenne muscular dystrophy (DMD) are rare conditions. Patients with X-linked SCID have pathogenic variants of the IL2RG gene, resulting in defective cellular and humoral immunity. DMD is also an X-linked condition caused by a dystrophin gene mutation, causing progressive proximal muscle weakness. We present a patient diagnosed with SCID at birth who underwent matched unrelated donor bone marrow transplant (BMT). Several months after, he was noted to have persistently elevated aminotransferases. Despite a lack of clinical signs of graft versus host disease (GvHD), a liver biopsy revealed mild GvHD. Creatine kinase (CK) levels of >19,000 U/L prompted evaluation for muscular dystrophies. Given BMT, genetic analysis was not an option. Muscle biopsy confirmed DMD. This case highlights the complexity of diagnosing and managing uncommon genetic conditions through a multidisciplinary team-based approach. This case is only the second reported case of SCID and DMD together.

PMID:37168752 | PMC:PMC10158261 | DOI:10.1097/PG9.0000000000000135