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Non-IgG Antibody Related Diseases

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IgA Related Diseases

IgA mostly originates from gut B cell responses to commensals, and IgA responses develop through highly complementary T cell-independent (TI) and T cell-dependent (TD) pathways. While TI-induced IgA broadly targets non-invasive commensals, TD-induced IgA coats penetrant commensals, and invasive pathogens. IgA can be detected in both gut mucosa and serum. In humans, intestinal IgA is dimeric, whereas serum IgA is largely monomeric. Intraluminal IgA, called secretory IgA (SIgA), further includes a pIgR-derived fragment termed the secretory component. This polypeptide covalently binds to SIgA to augment its stability and provide mucus-anchoring sites. Based on its characteristics, there are many diseases related to IgA, such as IgA nephropathy, dermatitis herpetiformis, celiac disease, inflammatory bowel disease (IBD), bullous disease, liver diseases, and sjögren's syndrome.

Impact of gut metabolites on gut IgA and systemic IgG responses. Fig.1 Impact of gut metabolites on gut IgA and systemic IgG responses. (Chen, 2020)

IgD Related Diseases

Although mostly known as a B cell antigen receptor, IgD also exists as a secreted antibody and, indeed, was first discovered in human sera. This IgD is released by IgM IgD+ plasma cells largely derived from mucosal B cells that have undergone IgM-to-IgD CSR. In humans, this process occurs in lymphoepithelial organs from the aerodigestive mucosa, including palatine and pharyngeal tonsils. In mice, IgM-to-IgD CSR has been detected in nasal-associated lymphoid tissue as well as in submandibular and mesenteric lymph nodes. Human IgM IgD+ plasma cells not only secrete IgD into the aerodigestive mucosa but also enter the circulation to seed the middle ear as well as the lachrymal, salivary and mammary glands. In diseases, IgD plays important role in hyper-IgD syndrome, autoimmune diseases, and multiple myeloma.

IgE Related Diseases

IgE antibody-induced inflammation is nearly synonymous with allergic disease, which affects one in five individuals worldwide. IgE is central to the mechanisms of immediate-type hypersensitivity reactions. These antibodies are also somewhat enigmatic given that a comprehensive understanding of IgE biology has yet to be established. IgE antibodies have gained significant attention as the incidence of allergic diseases has increased substantially. Atopic diseases are considered to be one of the principal manifestations of IgE-driven pathology. Allergen-specific IgE antibodies are bound to the surface of mast cells and basophils via Fc binding to the FceRI receptor. Allergen cross-linking of cell-bound IgE results in cellular degranulation and canonical symptoms of allergic inflammation. Immediate release of mediators causes rapid onset of vascular dilation and permeability, bronchoconstriction, leukocyte extravasation, and smooth muscle contraction. Cellular activation also results in synthetic processes which generate mediators of late-phase reactions. These processes result in clinical symptoms including potentially fatal anaphylaxis. Allergen-specific IgE can be utilized for diagnostics in allergy and is a target of therapies in asthma, environmental/food/venom allergies, and atopic dermatitis.

IgM Related Diseases

IgM is the most ancient member of our antibody family and the first antibody to appear during B cell ontogeny. IgM is also the first antibody released during a humoral response. Serum IgM forms pentamers associated with the joining chain and includes nonreactive IgM from conventional B cells, also termed B2 cells and polyreactive IgM from innate-like B1 cells. The latter IgM is readily detected in mice, but may also exist in humans. In general, IgM generates the first line of humoral defense against pathogens, but may also contribute to tissue homeostasis. Selective IgM deficiency, hyper IgM syndromes, and autoimmune disorders are all related to the IgM level of patients.

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All these diseases are clarifying the importance of non-IgG antibodies in researches. Recognizing the importance of non-IgG antibodies, Creative Biolabs has invested a lot of time, material, and human resources in non-IgG antibodies researches. With years of accumulation, we have established a comprehensive technology platform providing high-quality non-IgG antibody related services including but not limited to:

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  1. Chen, K.; et al. Rethinking mucosal antibody responses: IgM, IgG and IgD join IgA. Nat Rev Immunol. 2020, 20(7): 427-441.

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