Immunological Role of IgG Subclasses

Napodano, Cecilia; Marino, Maria; Stefanile, Annunziata; Pocino, Krizia; Scatena, Roberto; Gulli, Francesca; Rapaccini, Gian Lodovico; Noci, Stefano Delli; Capozio, Giovanna; Rigante, Donato; Basile, Umberto

doi:10.1080/08820139.2020.1775643

Cited by 42 publications

(39 citation statements)

References 84 publications

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“…Inflammatory response, and consequent ROS production, in these patients reduce semen total antioxidant capacity [ 32 ]. FLCs are a renowned marker of immune activation [ 12 ] and, in a first evaluation in a small cohort of patients with VAR, a reduced κ/λ ratio has been pointed out. We hinted at possible differential patterns in FLC expression between patients with an inflammatory seminal fluid and patients with VAR, the former having a relative prevalence of λ chains compared to the latter; we hypothesized that the low level of κ chains found in the VAR group could be caused by FLCs consumption, or else another signaling system rather than FLCs may be used to summon B cells in semen in VAR.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the detection of FLCs in biological fluids may be useful as a biomarker of inflammation or altered immune response, as is reported above. In several diseases, a differential FLCs production pattern in plasma, urine, saliva, cerebrospinal and synovial fluid has been shown [ 12 ]. Our group have determined, for the first time, their detectability in seminal fluid with higher λ FLCs in semen characterized by inflammation and lower κ FLCs in seminal fluid of patients affected by varicocele (VAR) compared to control group [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

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Inflammation and Oxidative Stress in Seminal Plasma: Search for Biomarkers in Diagnostic Approach to Male Infertility

Bruno

Basile

Vergani

et al. 2022

JPM

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Oxidative and inflammatory damage underlie several conditions related to male infertility, including varicocele. Free light chains of immunoglobulins (FLCs) are considered markers of low-grade inflammation in numerous diseases. Coenzyme Q10 (CoQ10), a lipidic antioxidant and anti-inflammatory compound, is involved in spermatozoa energy metabolism and motility. We aimed to evaluate FLCs’ seminal levels in patients with varicocele in comparison to control subjects and to correlate them with CoQ10 and Total Antioxidant Capacity (TAC) in human semen. Sixty-five patients were enrolled. Semen analysis was performed; patients were divided into three groups: controls, 12 normozoospermic patients, aged 34 (33–41) years; varicocele (VAR), 29 patients, aged 33 (26–37) years; and idiopathic, 24 oligo-, astheno- and oligoasthenozoospermic patients aged 37 (33.5–40.5) years. FLCs (κ and λ) were assayed by turbidimetric method; CoQ10 by HPLC; TAC by spectrophotometric method. λ FLCs showed a trend toward higher levels in VAR vs. controls and the idiopathic group. VAR showed a trend toward lower κ FLCs levels vs. the other two groups. When comparing κ/λ ratio, VAR showed significantly lower levels vs. controls and idiopathic. Moreover, CoQ10 seminal levels showed higher levels in VAR and idiopathic compared to controls. Data reported here confirm lower levels of κ/λ ratio in VAR and suggest a possible application in personalized medicine as clinical biomarkers for male infertility.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inflammation and Oxidative Stress in Seminal Plasma: Search for Biomarkers in Diagnostic Approach to Male Infertility

Bruno

Basile

Vergani

et al. 2022

JPM

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“…The reason could be the negative influence of trimodulin IgM species on phagocytosis, because IgM covers binding sites with high avidity [ 3 ] and therefore hampers IgG- or IgA-mediated phagocytosis. A further reason could be the higher portion of IgG4 in trimodulin, which has a lower ability to induce effector functions such as ADCP compared to IgG1 or IgG3 [ 91 , 105 , 106 ].…”

Section: Discussionmentioning

confidence: 99%

The Functional Role of IgA in the IgM/IgA-Enriched Immunoglobulin Preparation Trimodulin

et al. 2021

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In comparison to human immunoglobulin (Ig) G, antibodies of IgA class are not well investigated. In line with this, the functional role of the IgA component in IgM/IgA-enriched immunoglobulin preparations is also largely unknown. In recent years, powerful anti-pathogenic and immunomodulatory properties of human serum IgA especially on neutrophil function were unraveled. Therefore, the aim of our work is to investigate functional aspects of the trimodulin IgA component, a new plasma-derived polyvalent immunoglobulin preparation containing ~56% IgG, ~23% IgM and ~21% IgA. The functional role of IgA was investigated by analyzing the interaction of IgA with FcαRI, comparing trimodulin with standard intravenous IgG (IVIG) preparation and investigating Fc receptor (FcR)-dependent functions by excluding IgM-mediated effects. Trimodulin demonstrated potent immunomodulatory, as well as anti-pathogenic effects in our neutrophil model (neutrophil-like HL-60 cells). The IgA component of trimodulin was shown to induce a strong FcαRI-dependent inhibitory immunoreceptor tyrosine-based activation motif (ITAMi) signaling, counteract lipopolysaccharide-induced inflammation and mediate phagocytosis of Staphylococcus aureus. The fine-tuned balance between immunomodulatory and anti-pathogenic effects of trimodulin were shown to be dose-dependent. Summarized, our data demonstrate the functional role of IgA in trimodulin, highlighting the importance of this immunoglobulin class in immunoglobulin therapy.

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“…A different profile of serological IgG subclasses has been widely described in patients (pts) with autoimmune disorders (AD), increasing the interest to properly understand their contribution in pathogenesis and clinical significance for a different personalized management of disease [1]. IgG4 subclass represents the least frequent among IgG subclasses (about 5% of total IgG) and develops after prolonged activation of the immune system with or without antigen [2].…”

Section: Introductionmentioning

confidence: 99%

“…Sci. 2021, 22, x FOR PEER REVIEW 2 of 9 management of disease [1]. IgG4 subclass represents the least frequent among IgG subclasses (about 5% of total IgG) and develops after prolonged activation of the immune system with or without antigen [2].…”

Section: Introductionmentioning

confidence: 99%

Laboratory Investigation of Hybrid IgG4 k/λ in MuSK Positive Myasthenia Gravis

Basile

Napodano²,

Gulli³

et al. 2021

IJMS

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Myasthenia gravis with antibodies (Abs) against the muscle-specific tyrosine kinase (MuSK) is a rare autoimmune disorder (AD) of the neuromuscular junction (NMJ) and represents a prototype of AD with proven IgG4-mediated pathogenicity. Thanks to the mechanism of Fab-arm exchange (FAE) occurring in vivo, resulting MuSK IgG4 k/λ Abs increase their interference on NMJ and pathogenicity. The characterization of hybrid MuSK IgG4 as a biomarker for MG management is poorly investigated. Here, we evaluated total IgG4, hybrid IgG4 k/λ, and the hybrid/total ratio in 14 MuSK-MG sera in comparison with 24 from MG with Abs against acetylcholine receptor (AChR) that represents the not IgG4-mediated MG form. In both subtypes of MG, we found that the hybrid/total ratio reflects distribution reported in normal individuals; instead, when we correlated the hybrid/total ratio with specific immune-reactivity we found a positive correlation only with anti-MuSK titer, with a progressive increase of hybrid/total mean values with increasing disease severity, indirectly confirming that most part of hybrid IgG4 molecules are engaged in the anti-MuSK pathogenetic immune-reactivity. Further analysis is necessary to strengthen the significance of this less unknown biomarker, but we retain it is full of a diagnostic-prognostic powerful potential for the management of MuSK-MG.

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Immunological Role of IgG Subclasses

Cited by 42 publications

References 84 publications

Inflammation and Oxidative Stress in Seminal Plasma: Search for Biomarkers in Diagnostic Approach to Male Infertility

Inflammation and Oxidative Stress in Seminal Plasma: Search for Biomarkers in Diagnostic Approach to Male Infertility

The Functional Role of IgA in the IgM/IgA-Enriched Immunoglobulin Preparation Trimodulin

Laboratory Investigation of Hybrid IgG4 k/λ in MuSK Positive Myasthenia Gravis

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