Anti-IgG3 monoclonal antibody [DyLight® 650]

Chronic inflammatory demyelination polyneuropathy is a heterogeneous and treatable immune-mediated disorder that lacks biomarkers to support diagnosis. Recent evidence indicates that paranodal proteins (contactin 1, contactin-associated protein 1, and neurofascin-155) are the targets of autoantibodies in subsets of patients showing distinct clinical presentations. Here, we identified neurofascin-186 and neurofascin-140 as the main targets of autoantibodies in five patients presenting IgG reactivity against the nodes of Ranvier. Four patients displayed predominantly IgG4 antibodies, and one patient presented IgG3 antibodies that activated the complement pathway in vitro. These patients present distinct clinical features compared to those with anti-neurofascin-155 IgG4. Most patients had a severe phenotype associated with conduction block or decreased distal motor amplitude. Four patients had a subacute-onset and sensory ataxia. Two patients presented with nephrotic syndromes and one patient with an IgG4-related retroperitoneal fibrosis. Intravenous immunoglobulin and corticosteroids were effective in three patients, and one patient remitted following rituximab treatment. Clinical remission was associated with autoantibody depletion and with recovery of conduction block and distal motor amplitude suggesting a nodo-paranodopathy. Our data demonstrate that the pathogenic mechanisms responsible for chronic inflammatory demyelination polyneuropathy are broad and may include dysfunctions at the nodes of Ranvier in a subgroup of patients.

Objective: Given the emerging appreciation for the role of antibody-dependent effector functions and IgG subclass distribution among spontaneous controllers of HIV, we sought to determine whether antibody-associated features diverged in early HIV infection between patients who ultimately became controllers versus those who became progressors. Methods: IgG was purified from plasma from nine acutely infected patients who subsequently controlled HIV spontaneously (controllers) and 10 acutely infected individuals who did not control viremia (progressors). Antibody profiles were compared at weeks 4, 12, 24 and 48 postinfection. Levels of clade B gp120-specific, gp140-specific and gp41-specific IgG antibody subclasses were measured. In addition, gp120-specific antibody-dependent cellular phagocytosis, rapid fluorescent antibody-dependent cellular cytotoxicity and antibody-dependent cellular viral inhibition were all assessed. Results: Although no single antibody-related measurement was significantly associated with long-term HIV control, combinations of antibody-associated variables were able to accurately differentiate controllers and progressors. In contrast to controllers, progressors showed greater dynamic changes in gp120-specific subclass selection profiles, with increasing levels of Env-specific IgG2 antibodies and losses in Env-specific IgG3 antibodies. Moreover, progressors, but not controllers, lost antibody-dependent cellular viral inhibition function over time. Together, these results highlight changes in IgG subclass selection profiles in progressive, but not controlled, HIV infection. Conclusion: This study suggests that the temporal variation and maintenance of Envspecific IgG subclasses during acute HIV infection are predictive of eventual disease control. The maintenance of gp120-specific and gp140-specific IgG3 may contribute to control of disease in spontaneous controllers. Thus, strategies to induce stable IgG3 responses may preserve control of the viral reservoir. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.