Background
IgG1 is an important subclass of immunoglobulin G (IgG), one of the four subclasses found in humans. Immunoglobulins are antibodies produced by B cells that play a critical role in recognizing and neutralizing pathogens such as viruses and bacteria. IgG is the most abundant immunoglobulin type in serum, accounting for 70% to 75% of the total serum immunoglobulins, with IgG1 comprising about 66%, making it the most common subclass. IgG1 binds to antigens in the body, activating the complement system and triggering antibody-dependent cellular cytotoxicity (ADCC), mechanisms that are essential for fighting infections, clearing foreign substances, and targeting cancer cells. Two heavy chains and two light chains make up the IgG1 molecule. There are two types of light chains: lambda (λ) and kappa (κ). Either κ or λ light chains are present in every immunoglobulin molecule. Although κ and λ light chains typically do not differ significantly in their functions, some blood illnesses can cause an imbalance in their ratio, which can have substantial clinical ramifications. For instance, a significantly higher κ or λ ratio in the serum may be a sign of clonal proliferation, as shown in multiple myeloma or B-cell lymphomas, when B cells manufacture monoclonal antibodies with a fixed expression of either κ or λ light chains.
Multiple myeloma is a malignant blood cancer caused by the abnormal proliferation of plasma cells; the terminally differentiated cells of B cells responsible for producing antibodies. In multiple myeloma, abnormal plasma cells generate excessive monoclonal immunoglobulins, often resulting in elevated levels of a specific immunoglobulin subclass, such as IgG1 λ. The accumulation of these monoclonal antibodies in the body can lead to various symptoms, including bone damage, anemia, and hypercalcemia. In blood malignancies, detecting the expression of κ and λ light chains is crucial. The κ/λ ratio in healthy individuals usually remains within a balanced range. However, in multiple myeloma and certain B-cell lymphomas, this balance may be disrupted, leading to an overexpression of either κ or λ light chains. For patients with multiple myeloma, an increase in monoclonal IgG1 λ antibodies indicates the presence of clonal plasma cell disease, and assessing light chain expression helps physicians diagnose and stage these conditions.
Hyperviscosity syndrome (HVS) is another important complication associated with elevated IgG1 λ levels. HVS is caused by abnormally high concentrations of immunoglobulins in the serum, which increase blood viscosity and impair normal blood flow. Due to its large molecular size and unique structure, IgG1 λ immunoglobulins are particularly prone to raising blood viscosity, leading to HVS. Symptoms of HVS include headaches, blurred vision, fatigue, and nosebleeds, and in severe cases, it may cause more serious neurological complications. In multiple myeloma patients, the accumulation of IgG1 λ monoclonal antibodies can result in increased blood viscosity. Research has shown that IgG1 is the IgG subtype most closely linked to HVS, especially when present as high-concentration monoclonal antibodies. For example, in a case of multiple myeloma, a patient developed severe HVS due to high levels of IgG1 λ monoclonal proteins, leading to symptoms such as blurred vision and nosebleeds. Regular plasma exchange therapy (PEX) can lower immunoglobulin levels in the body, alleviate symptoms, and improve patients' quality of life. Overall, IgG1 λ immunoglobulins play a critical role in normal immune responses, but their abnormal expression often indicates the presence of hematological diseases. Particularly in the diagnosis and management of multiple myeloma and B-cell lymphomas, detecting IgG1 λ is essential for early diagnosis, disease staging, and monitoring treatment efficacy. Additionally, IgG1 λ is associated with serious complications like hyperviscosity syndrome, and timely diagnosis and intervention are vital for improving patient outcomes.
Alternative Names
Mouse IgG1 isotype control
IgG1 lambda control antibody
PE-conjugated IgG1 isotype control antibody
References
IgG Subclass Staining in Routine Renal Biopsy Material
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
Authors: Hemminger, Jessica; Nadasdy, Gyongyi; Satoskar, Anjali; Brodsky, Sergey V.; Nadasdy, Tibor
Abstract
Immunofluorescence staining plays a vital role in nephropathology, but the panel of antibodies used has not changed for decades. Further classification of immunoglobulin (Ig) G-containing immune-type deposits with IgG subclass staining (IgG1, IgG2, IgG3, and IgG4) has been shown to be of diagnostic utility in glomerular diseases, but their value in the evaluation of renal biopsies has not been addressed systematically in large renal biopsy material. Between January 2007 and June 2014, using direct immunofluorescence, we stained every renal biopsy for the IgG subclasses if there was moderate to prominent glomerular IgG staining and/or IgG-predominant or IgG-codominant glomerular staining. The total number of biopsies stained was 1084, which included 367 cases of membranous glomerulonephritis, 307 cases of lupus nephritis, 74 cases of fibrillary glomerulonephritis, 53 cases of proliferative glomerulonephritis with monoclonal IgG deposits, and 25 cases of antiglomerular basement membrane disease, among others. We found that monoclonality of IgG deposits cannot always be reliably determined on the basis of kappa and lambda light chain staining alone, particularly if concomitant (frequently nonspecific) IgM staining is present. In IgG heavy and heavy and light chain deposition disease (3 cases), subclass staining is very helpful, and in proliferative glomerulonephritis with monoclonal IgG deposits subclass staining is necessary. IgG subclass staining is useful in differentiating primary from secondary membranous glomerulonephritis. In proliferative glomerulonephritis with polyclonal IgG deposition, IgG1 dominance/codominance with concomitant IgG3 and IgG2 but weak or absent IgG4 staining favors an underlying autoimmune disease. IgG subclass staining is a very useful diagnostic method in a selected cohort of renal biopsies, particularly in biopsies with glomerulonephritis with monoclonal IgG deposits.
On the Perplexingly Low Rate of Transport of IgG2 across the Human Placenta
PLOS ONE
Authors: Einarsdottir, Helga K.; Stapleton, Nigel M.; Scherjon, Sicco; Andersen, Jan Terje; Rispens, Theo; van der Schoot, C. Ellen; Vidarsson, Gestur
Abstract
The neonatal receptor, FcRn, mediates both serum half-life extension as well as active transport of maternal IgG to the fetus during pregnancy. Therefore, transport efficiency and half-life go hand-in-hand. However, while the half-life of the human IgG2 subclass is comparable to IgG1, the placental transport of IgG2 is not, with the neonatal IgG1 levels generally exceeding maternal levels at birth, but not for IgG2. We hypothesized that the unique short-hinged structure of IgG2, which enables its kappa-, but not lambda-isotype to form at least three different structural isoforms, might be a contributing factor to these differences. To investigate whether there was any preference for either light chain, we measured placental transport of IgG subclasses as well as kappa/lambda-light chain isotypes of IgG1 and IgG2 in 27 matched mother-child pairs. We also studied the half-life of IgG1 and IgG2 light chain isotypes in mice, as well as that of synthesized IgG2 structural isotypes kappa A and kappa B. In order to investigate serum clearance of IgG1 and IgG2 light-chain isotypes in humans, we quantified the relative proportions of IgG1 and IgG2 light chains in hypogammaglobulinemia patients four weeks after IVIg infusion and compared to the original IVIg isotype composition. None of our results indicate any light chain preference in either of the FcRn mediated mechanisms; half-life extension or maternal transport.
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