References
1. D’Amico G. Natural history of idiopathic IgA nephropathy and factors
predictive of disease outcome. Seminars in nephrology.
2004;24(3):179-96.
2. Coppo R. Clinical and histological risk factors for progression of
IgA nephropathy: an update in children, young and adult patients.
Journal of nephrology. 2017;30(3):339-46.
3. Schena FP. A retrospective analysis of the natural history of primary
IgA nephropathy worldwide. The American journal of medicine.
1990;89(2):209-15.
4. Boyd JK, Cheung CK, Molyneux K, Feehally J, Barratt J. An update on
the pathogenesis and treatment of IgA nephropathy. Kidney international.
2012;81(9):833-43.
5. Lai KN. Pathogenesis of IgA nephropathy. Nature reviews Nephrology.
2012;8(5):275-83.
6. Magistroni R, D’Agati VD, Appel GB, Kiryluk K. New developments in
the genetics, pathogenesis, and therapy of IgA nephropathy. Kidney
international. 2015;88(5):974-89.
7. Suzuki H, Kiryluk K, Novak J, Moldoveanu Z, Herr AB, Renfrow MB,
Wyatt RJ, Scolari F et al. The pathophysiology of IgA nephropathy.
Journal of the American Society of Nephrology : JASN.
2011;22(10):1795-803.
8. Maecker HT, McCoy JP, Nussenblatt R. Standardizing immunophenotyping
for the Human Immunology Project. Nature reviews Immunology.
2012;12(3):191-200.
9. Mellis SJ, Baenziger JU. Structures of the O-glycosidically linked
oligosaccharides of human IgD. The Journal of biological chemistry.
1983;258(19):11557-63.
10. Smith AC, de Wolff JF, Molyneux K, Feehally J, Barratt J.
O-glycosylation of serum IgD in IgA nephropathy. Journal of the American
Society of Nephrology : JASN. 2006;17(4):1192-9.
11. Lai KN, Tang SC, Schena FP, Novak J, Tomino Y, Fogo AB, Glassock RJ.
IgA nephropathy. Nature reviews Disease primers. 2016;2:16001.
12. Kiryluk K, Novak J. The genetics and immunobiology of IgA
nephropathy. The Journal of clinical investigation. 2014;124(6):2325-32.
13. Vossenkamper A, Blair PA, Safinia N, Fraser LD, Das L, Sanders TJ,
Stagg AJ, Sanderson JD et al. A role for gut-associated lymphoid tissue
in shaping the human B cell repertoire. The Journal of experimental
medicine. 2013;210(9):1665-74.
14. Yeo SC, Cheung CK, Barratt J. New insights into the pathogenesis of
IgA nephropathy. Pediatric nephrology (Berlin, Germany).
2018;33(5):763-77.
15. Buren M, Yamashita M, Suzuki Y, Tomino Y, Emancipator SN. Altered
expression of lymphocyte homing chemokines in the pathogenesis of IgA
nephropathy. Contributions to nephrology. 2007;157:50-5.
16. Harper SJ, Pringle JH, Wicks AC, Hattersley J, Layward L, Allen A,
Gillies A, Lauder I. et al. Expression of J chain mRNA in duodenal IgA
plasma cells in IgA nephropathy. Kidney international.
1994;45(3):836-44.
17. Esteve Cols C, Graterol Torres FA, Quirant Sanchez B, Marco Rusinol
H, Navarro Diaz MI, Ara Del Rey J, Martinez Caceres EM. Immunological
Pattern in IgA Nephropathy. International journal of molecular sciences.
2020;21(4).
18. Si R, Zhao P, Yu Z, Qu Z, Sun W, Li T, Jiang Y. Increased
Non-switched Memory B Cells are Associated with Plasmablasts, Serum IL-6
Levels and Renal Functional Impairments in IgAN Patients. Immunological
investigations. 2019:1-13.
19. Arumugakani G, Stephenson SJ, Newton DJ, Rawstron A, Emery P, Doody
GM, McGonagle D, Tooze RM. Early Emergence of CD19-Negative Human
Antibody-Secreting Cells at the Plasmablast to Plasma Cell Transition.
Journal of immunology (Baltimore, Md : 1950). 2017;198(12):4618-28.
20. Hiepe F, Radbruch A. Plasma cells as an innovative target in
autoimmune disease with renal manifestations. Nature reviews Nephrology.
2016;12(4):232-40.
21. Landsverk OJ, Snir O, Casado RB, Richter L, Mold JE, Reu P,
Horneland R, Paulsen V. et al. Antibody-secreting plasma cells persist
for decades in human intestine. The Journal of experimental medicine.
2017;214(2):309-17.
22. Huang JL, Woolf AS, Kolatsi-Joannou M, Baluk P, Sandford RN, Peters
DJ, McDonald DM, Price KL. et al. Vascular Endothelial Growth Factor C
for Polycystic Kidney Diseases. Journal of the American Society of
Nephrology : JASN. 2016;27(1):69-77.
23. Ziegler-Heitbrock L, Hofer TP. Toward a refined definition of
monocyte subsets. Frontiers in immunology. 2013;4:23.
24. Hijdra D, Vorselaars AD, Grutters JC, Claessen AM, Rijkers GT.
Phenotypic characterization of human intermediate monocytes. Frontiers
in immunology. 2013;4:339.
25. Cox SN, Serino G, Sallustio F, Blasi A, Rossini M, Pesce F, Schena
FP. Altered monocyte expression and expansion of non-classical monocyte
subset in IgA nephropathy patients. Nephrology, dialysis,
transplantation : official publication of the European Dialysis and
Transplant Association - European Renal Association.
2015;30(7):1122-232.
26. Wallquist C, Paulson JM, Hylander B, Lundahl J, Jacobson SH.
Increased accumulation of CD16+ monocytes at local sites of inflammation
in patients with chronic kidney disease. Scandinavian journal of
immunology. 2013;78(6):538-44.
27. Zhu H, Hu F, Sun X, Zhang X, Zhu L, Liu X, Li X, Xu L. et al.
CD16(+) Monocyte Subset Was Enriched and Functionally Exacerbated in
Driving T-Cell Activation and B-Cell Response in Systemic Lupus
Erythematosus. Frontiers in immunology. 2016;7:512.
28. Schwabe RF, Engelmann H, Hess S, Fricke H. Soluble CD40 in the serum
of healthy donors, patients with chronic renal failure, haemodialysis
and chronic ambulatory peritoneal dialysis (CAPD) patients. Clinical and
experimental immunology. 1999;117(1):153-8.
29. van Kooten C, Gaillard C, Galizzi JP, Hermann P, Fossiez F,
Banchereau J, Blanchard D. B cells regulate expression of CD40 ligand on
activated T cells by lowering the mRNA level and through the release of
soluble CD40. European journal of immunology. 1994;24(4):787-92.
30. Bjorck P, Braesch-Andersen S, Paulie S. Antibodies to distinct
epitopes on the CD40 molecule co-operate in stimulation and can be used
for the detection of soluble CD40. Immunology. 1994;83(3):430-7.
Figure legends
Figure. 1 Gating strategies for analysis of CD3- CD19+ CD27-
IgD+ naïve B cells, CD3- CD19+ CD27+ IgD+ pre-switched B cells, CD3-
CD19+ CD27+ IgD- switched B cells, CD3- CD19- CD27 hiCD38 hi long-lived plasma cells and monocyte subsets.
Figure 2. Proportions of B cell subsets in patients with IgA
nephropathy (IgAN), autosomal dominant polycystic kidney disease (ADPKD)
and in healthy controls (HC). Comparisons for cell fractions were
performed using the Kruskal-Wallis test, P < 0.05 was
considered statistically significant. Scatter plots represent the range
with whiskers and the median as the middle line.
Figure 3. Ratio of naïve/pre-switched B cells in patients with
IgA nephropathy (IgAN), autosomal dominant polycystic kidney disease
(ADPKD) and healthy controls (HC). Comparisons for cell fractions were
performed using the Kruskal-Wallis test, P < 0.05 was
considered statistically significant. Scatter plots represent the range
with whiskers and the median as the middle line.
Figure 4. Proportions of non-classical monocytes in patients
with IgAN, ADPKD and HC. Comparisons for cell fractions were performed
using the Kruskal-Wallis test, P < 0.05 was considered
statistically significant. Scatter plots represent the range with
whiskers and the median as the middle line.
Figure 5. Levels of cytokines in plasma from IgAN patients and
healthy controls. Mann-Whitney U test was used to compare cytokine
concentrations, P < 0.05 was considered statistically
significant. Scatter plots represent the range with whiskers and the
median as the middle line.
Figure 6. The relationship between MCP-1 / sCD40L levels and
albuminuria in IgAN patients using linear regression test.
Figure 7. The relationship between cytokines and immune cell
subtypes in IgAN patients using linear regression test.
Table 1 Demographic characteristics of study subjects.