heavy chain deposition disease in kidney biopsies
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Heavy chain deposition disease in kidney biopsies
Alenka Vizjak, Jerica Mraz, Jelka Lindič, Dušan Ferluga
Institute of Pathology, Faculty of Medicine University of Ljubljana, Slovenia
Disclosures: no conflicts of interest
Heavy chain deposition disease
(HCDD) • HCDD - a rare monoclonal immunoglobulin-
related disorder of not yet fully explored pathogenesis
• Characterized by production and systemic deposition of structurally abnormal immunoglobulin heavy chains, while light chains absent in the deposits
• First described by Aucouturier et al(N Engl J Med 1993; 329: 1389-93)
Monoclonal immunoglobulin deposits in the kidney
Amyloid deposits
Non-amyloid monoclonal immunoglobulin deposits
Amyloidosis LC
HC (very rare)
MIDD Randall-type
LCDD
LHCDD
HCDD
GN with monoclonal Igs dps mimicking IC-GN
Cryoglobulinemic-GN
Immunotactoid GP / fibrillary GN
Patients and methods
• 4 biopsy cases of HCDD (5 kidney biopsies; 1 autopsy), representing 0.09% prevalence among 5481 native kidney biopsies
• All 4 female patients, age range 62 – 79 yrs, mean age 73.0 yrs
• Standard light microscopy• Immunofluorescence microscopy
IgA, IgG, IgM, κ, λ, C3, C1q, fibrin/fibrinogen, albuminIgG1, IgG2, IgG3, IgG4, γCH1, γCH2, γCH3
• Electron microscopy
Clinical presentation / diagnosis in 4 patients with HCDD
Pts At kidney biopsy After kidney biopsy
PM - 1st CKD, prot, compl↓ no dysproteinemia
PM - 2nd CKD, NS, compl↓ no dysproteinemia
JA CKD, prot, compl↓ plasmocytoma
BŠ RPGN, NS, compl↓ plasmocytoma
RM CKD, nephr prot, compl norm
no dysproteinemia
CKD – chronic kidney disease, NS – nephrotic syndrome
Immunofluorescence microscopy in 4 cases of HCDD
Pts IgG (γ)
IgGsubclass
γCH1 γCH2γCH3
κ / λ C3 C1q
PM - 1st 4+ n.d. n.d. n.d. 2+ / ± 2+ 4+
PM - 2nd 4+ IgG3 0 4+ 0 / 0 2+ 4+
JA 3+ IgG3 0 3+ 0 / 0 4+ 3+
BŠ 4+ IgG3 0 4+ 0 / 0 3+ 4+
RM 4+ IgG1 0 4+ 0 / 0 4+ 3+
Light and electron microscopy in 4 cases with HCDD
Light microscopy•Diffuse nodular glomerulosclerosis 4/4•Glomerular capillary aneurysms 4/4•Mesangial proliferation, 4/4with segm endo-, membranoprol pattern 3/4•Extracapillary crescents (few) 2/4
Electron microscopy•Punctate and powdery electron dense deposits 3/4
IgG (γ heavy chain) κ, λ light chains
IgG (γ heavy chain)
IgG1 IgG2
C3 C1q
γCH1 γCH2
SMA+CD31 CD68
Conclusions of our study
• Immunofluorescence examination of kidney biopsy, including testing for Igs heavy and light chains, as well as IgG subclasses, is crucial for the diagnosis of HCDD.
• Our study showed that HCDD is peculiar among MIDD because of uniform pattern of nodular glomerulosclerosis with pronounced capillary aneurysms and significant proliferation due to complement activation.
• Constant deletion of the gamma heavy chain CH1 domain and its significance in the pathogenesis of HCDD was confirmed.
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