Increased levels of circulating class-switched memory B cells and plasmablasts are associated with serum immunoglobulin G in primary focal segmental glomerulosclerosis patients

Abstract Background Some renal biopsies cannot distinguish minimal change disease (MCD) from primary focal segmental glomerulosclerosis (FSGS) because of inadequate sampling and/or a lack of sampled glomeruli with segmental sclerosis. As protein excretion in MCD has been described as being albumin-selective, we examined whether the ratio of immunoglobulin G (IgG)/albumin staining in protein reabsorption droplets (tPRD) might help distinguish MCD from FSGS. Methods Frozen tissue from 144 native renal biopsies from patients with nephrotic syndrome and a diagnosis of MCD or FSGS [73 MCD, 30 FSGS tip variant (FSGS-tip), 38 FSGS-not otherwise specified (FSGS-NOS), 3 FSGS collapsing] was retrospectively stained by direct immunofluorescence for IgG and albumin; none of these samples showed diagnostic lesions of FSGS. IgG and albumin staining of tPRD were graded on a scale of 0 to 3+ based on the distribution and intensity of staining. Results Mean (standard deviation) IgG/albumin staining ratios were 0.186 ± 0.239 for MCD, 0.423 ± 0.334 for FSGS-tip (P = 0.0001 versus MCD) and 0.693 ± 0.297 for FSGS-NOS (P < 0.0001 versus MCD; P = 0.0001 versus FSGS-tip). Of 84 biopsies with a ratio ≤0.33, 63 (75%) showed MCD, whereas among 21 with a ratio of 1.0, all but one showed FSGS (15 FSGS-NOS). Conclusions In summary, IgG/albumin staining in tPRD was correlated with histologic diagnosis in renal biopsies with MCD and FSGS. A ratio of ≤0.33 was associated with MCD, whereas a ratio of 1.0 was most often seen with FSGS-NOS.

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Natural occurrence and origin of somatically mutated memory B cells in mice.

Journal of Experimental Medicine ◽

10.1084/jem.176.2.427 ◽

1992 ◽

Vol 176 (2) ◽

pp. 427-438 ◽

Cited By ~ 52

Author(s):

B Schittek ◽

K Rajewsky

Keyword(s):

B Cells ◽

B Cell ◽

Immunoglobulin G ◽

Memory B Cells ◽

Antibody Repertoire ◽

Natural Occurrence ◽

Cell Pool ◽

Vh Genes ◽

Environmental Antigens ◽

Delta Cells

While most murine peripheral B cells express germline-encoded antibodies of classes M and D (mu+ delta+ cells), small numbers of memory B cells expressing somatically mutated immunoglobulin G antibodies are generated upon T cell-dependent immunization. Analyzing the antibody repertoire of the mu-delta- B cell pool in unimmunized mice, we show that these cells express somatically mutated VH genes and that most of these genes derive from a set of germline VH genes dominantly expressed by mu+delta+ B cells. Thus, class-switched memory B cells are generated in the absence of intentional immunization, presumably in response to environmental antigens. These cells are either recruited from mu+delta+ B cells or selected from newly arising B cells in parallel to the latter, by the same antigens.

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Deficiency of Somatic Hypermutation of Immunoglobulin G Transcripts Is a Better Predictor of Severe Respiratory Tract Infections than Lack of Memory B Cells in Common Variable Immunodeficiency

Journal of Clinical Immunology ◽

10.1007/s10875-005-5034-x ◽

2005 ◽

Vol 25 (4) ◽

pp. 392-403 ◽

Cited By ~ 15

Author(s):

Lone Schejbel ◽

Hanne Marquart ◽

Vagn Andersen ◽

Henrik Permin ◽

Pernille Andersen ◽

...

Keyword(s):

B Cells ◽

Respiratory Tract ◽

Immunoglobulin G ◽

Common Variable Immunodeficiency ◽

Respiratory Tract Infections ◽

Somatic Hypermutation ◽

Memory B Cells ◽

Tract Infections ◽

Common Variable

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T and B cells immunophenotypes in blood and urine of patients with focal segmental glomerulosclerosis in relation to disease severity

Clinical Practice ◽

10.4172/clinical-practice.1000414 ◽

2018 ◽

Vol 15 (5) ◽

Author(s):

Sabiha Anis ◽

Ejaz Ahmed ◽

Rana Muzaffar ◽

Syed Adibul Hasan Rizv

Keyword(s):

B Cells ◽

Disease Severity ◽

Focal Segmental Glomerulosclerosis ◽

T And B Cells ◽

Segmental Glomerulosclerosis

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Rituximab Therapy for Adults with Nephrotic Syndromes: Standard Schedules or B Cell-Targeted Therapy?

Journal of Clinical Medicine ◽

10.3390/jcm10245847 ◽

2021 ◽

Vol 10 (24) ◽

pp. 5847

Author(s):

Lucia Del Vecchio ◽

Marco Allinovi ◽

Paolo Rocco ◽

Bruno Brando

Keyword(s):

B Cells ◽

B Cell ◽

Focal Segmental Glomerulosclerosis ◽

Membranous Nephropathy ◽

Minimal Change Disease ◽

Minimal Change ◽

Segmental Glomerulosclerosis ◽

Steroid Dependent ◽

B Cell Subsets ◽

Anti Cd20

Rituximab is a chimeric anti-CD20 monoclonal antibody. It acts mainly through complement-dependent cytotoxicity on B cells expressing the CD20 marker. In this review, we analyse the efficacy and possible pitfalls of rituximab to treat nephrotic syndromes by taking into account pharmacological considerations and CD19 marker testing utility. Despite the fact that the drug has been in use for years, efficacy and treatment schedules in adults with nephrotic syndrome are still a matter of debate. Clinical trials have proven the efficacy and safety of rituximab in idiopathic membranous nephropathy. Data from observational studies also showed the efficacy of rituximab in minimal change disease and focal segmental glomerulosclerosis. Rituximab use is now widely recommended by new Kidney Disease Improved Outcome (KDIGO) guidelines in membranous nephropathy and in frequent-relapsing, steroid-dependent minimal change disease or focal segmental glomerulosclerosis. However, rituximab response has a large interindividual variability. One reason could be that rituximab is lost in the urine at a higher extent in patients with nonselective nephrotic proteinuria, exposing patients to different rituximab plasma levels. Moreover, the association between CD19+ levels and clinical response or relapses is not always present, making the use of this marker in clinical practice complex. High resolution flow cytometry has increased the capability of detecting residual CD19+ B cells. Moreover, it can identify specific B-cell subsets (including IgG-switched memory B cells), which can repopulate at different rates. Its wider use could become a useful tool for better understanding reasons of rituximab failure or avoiding unnecessary retreatments.

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