Low‐affinity immunoglobulin gamma Fc region receptor III‐B (FcγRIIIB, CD16B) deficiency in patients with blood and immune system disorders

Minguela, Alfredo; Salido, Eduardo; Soto-Ramírez, María F; Montes-Ares, Olga; Leal, Juan D; García-Garay, María C; Periago, Adela; Berenguer, M; Blanque, Miguel; Campillo, José A.

doi:10.1111/bjh.17828

Cited by 3 publications

(5 citation statements)

References 14 publications

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“…Interestingly, herpesvirus infections, but not a-CoV infections, also elicited downregulation of leukocyte-mediated immunity and upregulation of mitogen-activated protein kinase (MAPK) cascades and the inflammatory and humoral response. Besides the particularity of herpesviruses to persist in the host as latent infections (80), studies suggest that bat responses to DNA viruses are dampened in contrast to RNA viruses (15,16,104), potentially explaining our observed patterns. DNA viruses are known to usurp the MAPK signaling pathway to exploit DNA replication machinery, induce cell proliferation, and prevent cell death in response to pathogen recognition (105).…”

Section: Discussionmentioning

confidence: 81%

“…Vampire bats likely respond to herpesvirus infections in multiple ways, possibly due to the ability of these viruses to persist as latent infections that can reactivate periodically ( 80 ). By increasing abundance of FCGR2B, bats are apparently mounting humoral immune responses against herpesviruses, as this protein is expressed in mature neutrophils in charge of removing spontaneously forming immune complexes to dampen Fc-dependent immune reactions ( 81 ). This mechanism may possibly arise to prevent the potentially toxic side effects of systemic innate interferon (IFN) responses, especially important for chronic infections or secondary exposure to the virus ( 82 ).…”

Section: Discussionmentioning

confidence: 99%

“…When focusing on strict biomarkers in this analysis, we confirmed the same seven proteins for a-CoVs as in our prior study (33) and added eight (positive biomarkers: FCGR2B, PAFAH1B2, RNASE4, TSPAN2, and VNN3; negative biomarkers: AMY2A, LDHB, and LMNA) for herpesvirus infections and two (F5 and TCN2, both positive) for hemoplasma infections. Vampire bats likely respond to herpesvirus infections in multiple ways, possibly due to the ability of these viruses to persist as latent infections that can reactivate periodically (80). By increasing abundance of FCGR2B, bats are apparently mounting humoral immune responses against herpesviruses, as this protein is expressed in mature neutrophils in charge of removing spontaneously forming immune complexes to dampen Fc- dependent immune reactions (81).…”

Section: Discussionmentioning

confidence: 99%

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Serum proteomics reveals a tolerant immune phenotype across multiple pathogen taxa in wild vampire bats

Vicente-Santos,

Lock,

Allira

et al. 2023

Front. Immunol.

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Bats carry many zoonotic pathogens without showing pronounced pathology, with a few exceptions. The underlying immune tolerance mechanisms in bats remain poorly understood, although information-rich omics tools hold promise for identifying a wide range of immune markers and their relationship with infection. To evaluate the generality of immune responses to infection, we assessed the differences and similarities in serum proteomes of wild vampire bats (Desmodus rotundus) across infection status with five taxonomically distinct pathogens: bacteria (Bartonella spp., hemoplasmas), protozoa (Trypanosoma cruzi), and DNA (herpesviruses) and RNA (alphacoronaviruses) viruses. From 19 bats sampled in 2019 in Belize, we evaluated the up- and downregulated immune responses of infected versus uninfected individuals for each pathogen. Using a high-quality genome annotation for vampire bats, we identified 586 serum proteins but found no evidence for differential abundance nor differences in composition between infected and uninfected bats. However, using receiver operating characteristic curves, we identified four to 48 candidate biomarkers of infection depending on the pathogen, including seven overlapping biomarkers (DSG2, PCBP1, MGAM, APOA4, DPEP1, GOT1, and IGFALS). Enrichment analysis of these proteins revealed that our viral pathogens, but not the bacteria or protozoa studied, were associated with upregulation of extracellular and cytoplasmatic secretory vesicles (indicative of viral replication) and downregulation of complement activation and coagulation cascades. Additionally, herpesvirus infection elicited a downregulation of leukocyte-mediated immunity and defense response but an upregulation of an inflammatory and humoral immune response. In contrast to our two viral infections, we found downregulation of lipid and cholesterol homeostasis and metabolism with Bartonella spp. infection, of platelet-dense and secretory granules with hemoplasma infection, and of blood coagulation pathways with T. cruzi infection. Despite the small sample size, our results suggest that vampire bats have a similar suite of immune mechanisms for viruses distinct from responses to the other pathogen taxa, and we identify potential biomarkers that can expand our understanding of pathogenesis of these infections in bats. By applying a proteomic approach to a multi-pathogen system in wild animals, our study provides a distinct framework that could be expanded across bat species to increase our understanding of how bats tolerate pathogens.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Serum proteomics reveals a tolerant immune phenotype across multiple pathogen taxa in wild vampire bats

Vicente-Santos,

Lock,

Allira

et al. 2023

Front. Immunol.

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“… 21 Excessive neutrophil activation and the production of large quantities of cytolytic and pro-inflammatory chemicals are possible consequences of the interaction of IgG-containing immunoglobulins with FcγRIIIb, which may result in severe tissue damage. 22 , 23 The CD16b receptor is released from the surface of leukocytes when they are activated in an inflammatory environment. 24 Many investigations have shown a significant association between CD16b gene polymorphisms and SLE susceptibility.…”

Section: Discussionmentioning

confidence: 99%

Elevated activating Fc gamma receptors levels correlated with susceptibility and severity of IgA nephropathy

Liu

Yu³

et al. 2022

Therapeutic Advances in Chronic Disease

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Background: It is still uncertain if a dysregulated expression of activating Fc gamma receptors (FcγRs) is associated with the development of immunoglobulin A nephropathy (IgAN). Methods: RNA sequencing was used to determine the mRNA levels of type I FcγRs, which were then verified by quantitative reverse transcription–polymerase chain reaction (qRT-PCR). Commercial ELISA kits were used to detect plasma soluble FcγRIIIb (sFcγRIIIb). Results: We first examined the expression of FcγRs genes in 17 patients with IgAN and six healthy controls. The expression of FcγRIa, FcγRIb, FcγRIIa, FcγRIIc, FcγRIIIa, and FcγRIIIb was shown to be higher in IgAN patients. Even without statistical significance, there was a downward trend in FcγRIIb mRNA levels in IgAN. We observed that the expression levels of activating FcγR mRNAs were consistently higher in an independent set of 20 IgAN patients and 20 healthy controls, confirming the RNA-seq results. FcγRIIIb was the IgG receptor with the greatest difference in expression between the two groups (log2 fold-change = 1.82). We observed a much higher percent of FcγRIIIb positive cells in IgAN by flow cytometry. Next, we measured plasma sFcRIIIb levels in 50 patients with IgAN and 50 healthy controls. The findings revealed that the mean sFcγRIIIb level in plasma in participants with IgAN was much higher than that of healthy controls. Increased sFcγRIIIb levels were associated with a substantial increase in body mass index (BMI), lipid levels, serum creatinine level, and a larger percentage of sclerosis compared with lower sFcRIIIb levels. Patients in the group with higher sFcγRIIIb levels were more likely to get glucocorticoid treatment. Conclusion: The results demonstrated that the mRNA levels of the activating Fc receptor of IgG were significantly increased in IgAN. Patients with higher plasma sFcγRIIIb levels may have had more severe illness than those with lower levels.

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“…The Fc-gamma-receptor-IIIb (FcγRIIIb; CD16b) is an immunogenic and polymorphic neutrophil glycoprotein encoded by the FCGR3B gene. In the first domain of the glycoprotein, the human neutrophil antigen-1 (HNA-1) system is expressed, comprising four antigenic epitopes: HNA-1a, HNA-1b, HNA-1c and HNA-1d, encoded by three alleles (FCGR3B*01, FCGR3B*02 and FCGR3B*03) [1][2][3][4].…”

Section: Introductionmentioning

confidence: 99%

Analysis of maternal Fc gamma receptor IIIb isoantibodies using immunomagnetic negative selected neutrophils

Martins,

Moritz,

Abbas

et al. 2024

Vox Sanguinis

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Background and ObjectivesThe isolation of neutrophils and subsequent detection of anti‐human neutrophil antigens (HNA) antibodies are crucial in clinical medicine for the diagnosis of autoimmune neutropenia, neonatal alloimmune neutropenia (NAIN) and transfusion‐related acute lung injury (TRALI). This study reports two cases of maternal anti‐Fc‐gamma‐receptor‐IIIb (FcγRIIIb) isoimmunization without NAIN symptoms and compares the efficiency of immunomagnetic negative selection (IMNS) with traditional dextran/Ficoll for neutrophil isolation in HNA serological assays.Materials and MethodsInvestigating two cases of maternal anti‐FcγRIIIb isoimmunization, neutrophils from three donors were isolated from 8 mL of whole blood using IMNS and dextran/Ficoll. Serological assays included the granulocyte agglutination and immunofluorescence test, monoclonal antibody immobilization of granulocyte antigens and the LABScreen Multi (One Lambda). IMNS and dextran/Ficoll were compared in terms of cell yield, viability, time, cost and purity.ResultsMaternal anti‐FcγRIIIb isoantibodies with FCGR3B gene deletion were detected in both cases. Newborns and fathers exhibited specific gene combinations: FCGR3B*02/FCGR3B*02 (Case 1) and FCGR3B*02/FCGR3B*03 (Case 2). IMNS outperformed dextran/Ficoll, yielding four times more neutrophils (average neutrophil counts: 18.5 × 103/μL vs. 4.5 × 103/μL), efficiently removing non‐neutrophil cells and reducing processing time (30–40 min vs. 70–90 min), although it incurred a higher cost (2.7 times).ConclusionTwo cases of maternal anti‐FcγRIIIb isoantibodies, unrelated to NAIN, were identified. Although neutropenia has not been described in these cases, we emphasize the importance of identifying asymptomatic cases with the potential for severe neutropenia. Additionally, IMNS is introduced as a rapid, high‐yield, high‐purity neutrophil isolation technique, beneficial for serological assays detecting anti‐HNA antibodies.

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Low‐affinity immunoglobulin gamma Fc region receptor III‐B (FcγRIIIB, CD16B) deficiency in patients with blood and immune system disorders

Cited by 3 publications

References 14 publications

Serum proteomics reveals a tolerant immune phenotype across multiple pathogen taxa in wild vampire bats

Serum proteomics reveals a tolerant immune phenotype across multiple pathogen taxa in wild vampire bats

Elevated activating Fc gamma receptors levels correlated with susceptibility and severity of IgA nephropathy

Analysis of maternal Fc gamma receptor IIIb isoantibodies using immunomagnetic negative selected neutrophils

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