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.