OBJECTIVE To investigate the dynamics of IgG1 and IgG4 anti-citrullinated protein antibody (ACPA) subclasses during anti-tumour necrosis factor (TNF) treatment in patients with rheumatoid arthritis (RA). METHODS IgG, IgG1 and IgG4 ACPA levels were determined by ELISA on anti-citrullinated fibrinogen (ACF) and IgG1 : IgG4 ACPA ratios were calculated. A pilot study was performed in 28 ACF-posit...

Pemphigus vulgaris (PV) is characterized by IgG1 and IgG4 autoantibodies to desmoglein (Dsg) 3, causing suprabasal blistering of skin and mucous membranes. IgG4 is the dominant autoantibody subclass in PV and correlates with disease activity, whereas IgG1 can be associated with remittent disease. It is unknown if switching the same variable region between IgG4 and IgG1 directly impacts pathogen...

During antigen-induced immune responses, human B cells switch isotype from immunoglobulin M (IgM)-IgD to IgG1-4, IgA1-2, or IgE. In the human, no cytokines have yet been demonstrated to act as switch factors for IgG1, IgG2, and IgG3. In this paper, we report that in response to interleukin 10 (IL-10), anti-CD40 activated tonsillar surface IgD+ (sIgD+) B cells are induced to secrete large amount...

Type-specific IgG1 and IgG2 antibodies to Streptococcus pneumoniae capsular polysaccharides 14 and 19F were measured in cord blood samples from 425 neonates, to determine which antibody subclass was most strongly associated with otitis media (OM) during the first 6 months of life (early OM). Early OM was significantly associated with type 14 IgG1 antibody in the lowest antibody quartile (P=.055...

PURPOSE Recent studies have revealed that fucose removal from the oligosaccharides of human IgG1 antibodies results in a significant enhancement of antibody-dependent cellular cytotoxicity (ADCC) via improved IgG1 binding to FcgammaRIIIa. In this report, we investigated the relationship between enhanced ADCC and antigen density on target cells using IgG1 antibodies with reduced fucose. EXPERI...

We analyzed the effect of isotype variation on effectiveness of B-cell CD19 immunotoxins (IT) by using class switch variants (CLB-B4-IgG1 and CLB-B4-IgG2a) conjugated to ricin A. Notably, IgG1-IT appeared to be approximately 100-fold more potent than IgG2a-IT toward B-cell lines Daudi and KM3. Binding and internalization studies with 125I-labeled monoclonal antibodies (mAbs) revealed a higher c...

Ab-based therapies have undergone a renaissance in recent years, but infusion-related reactions are a significant clinical problem. Administration of certain mAbs to Swiss Webster mice infected with Cryptococcus neoformans can result in acute lethal toxicity (ALT) characterized by cardiovascular collapse. The ability of a mAb to produce ALT is isotype dependent and occurs with IgG1 but not IgG3...

After albumin, immunoglobulin G (IgG) are the most abundant proteins in human serum, with IgG1 and IgG3 being the most abundant subclasses directed against protein antigens. The quality of the IgG-Fc-glycosylation has important functional consequences, which have been found to be skewed toward low fucosylation in some antigen-specific immune responses. This increases the affinity to IgG1-Fc-rec...

Humanized antibodies are likely to have a major role in therapy and it is important to define their interaction with physiological effectors. By comparing a matched series of chimeric human mAbs we found that igG1 was most efficient in complement lysis, although IgG3 bound more C1q. To resolve this paradox we compared the ability of human IgG1, IgG2, IgG3, IgG4, and IgE and rat IgG2b to cause C...