Stains & CD markers
DNAJB9
Copyright: 2021-2025, PathologyOutlines.com, Inc.
PubMed Search: DNAJB9
DNAJB9
Board of reviewers: Alexei Mikhailov, M.D., Ph.D.
Editorial Board Member: Christian M. Schürch, M.D., Ph.D.
Last author update: 22 April 2025
Last staff update: 22 April 2025
Copyright: 2021-2025, PathologyOutlines.com, Inc.
PubMed Search: DNAJB9
Table of Contents
Definition / general | Essential features | Terminology | Pathophysiology | Interpretation | Uses by pathologists | Prognostic factors | Microscopic (histologic) description | Microscopic (histologic) images | Positive staining - normal | Positive staining - disease | Negative staining | Sample pathology report | Practice question #1 | Practice answer #1 | Practice question #2 | Practice answer #2Cite this page: Fossati E, L'Imperio V. DNAJB9. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsdnajb9.html. Accessed April 29th, 2025.
Definition / general
- DnaJ heat shock protein family (Hsp40), subfamily B, member 9 (DNAJB9) is a 26 kDa highly conserved and ubiquitous protein that is involved in protein folding and detection of endoplasmic reticulum (ER) stress (Kidney360 2020;1:1002)
- Due to its high specificity for the detection of fibrillary glomerulonephritis in nephropathology, its use as a diagnostic marker has become more frequent in recent years
Essential features
- DNAJB9 is a heat shock protein (HSP) involved in protein folding, refolding, protein quality control and the detection of endoplasmic reticulum stress
- Although it is physiologically ubiquitous, it is mainly expressed in cells with a developed endoplasmic reticulum
- Overproduced in fibrillary glomerulonephritis (FGN), showing a typical smudgy extracellular stain
- DNAJB9 immunohistochemistry (IHC) can show granular cytoplasmic stain but without the smudgy extracellular signal in normal tissues and in other glomerulonephritis
Terminology
- DnaJ heat shock protein family (Hsp40), subfamily B, member 9 (DNAJB9)
- Synonyms: microvascular endothelial differentiation gene 1 (MDG1; MDG-1); ER resident protein ERdj4
Pathophysiology
- DNAJB9 is an HSP involved in folding, refolding and protein quality control as a cochaperone of HSP70
- J domain is made of the histidine - proline - aspartic acid sequence and promotes ATP hydrolysis (Kidney360 2020;1:1002)
- Detects endoplasmic reticulum stress in order to activate endoplasmic reticulum associated degradation (ERAD) and the unfolded protein response (UPR) pattern (Kidney360 2020;1:1002)
- Selective repressor of inositol requiring enzyme 1 (IRE1) when the endoplasmic reticulum is not stressed, which leads to the suppression of UPR
- In an endoplasmic reticulum stressed state, the unfolded proteins compete with DNAJB9, therefore the UPR pattern is activated
- Downregulates the proapoptotic function of p53 (Cell Death Differ 2015;22:86)
- Due to its ubiquity, it has been studied in several conditions such as B cell development and function, hepatitis C virus (HCV) related conditions, insulin metabolism, metabolic defects and fibrillary glomerulonephritis (Cell Mol Life Sci 2021;79:9)
- Overproduced in fibrillary glomerulonephritis, especially in the glomeruli; the role of DNAJB9 in this condition is still elusive (Cell Mol Life Sci 2021;79:9)
Interpretation
- DNAJB9 is expressed in all healthy tissues, showing in IHC as a variable (often weak) fine to coarsely granular cytoplasmic stain without extracellular stain (Kidney Int Rep 2017;3:56)
- Intense smudgy extracellular stain is considered the positive staining pattern in fibrillary glomerulonephritis (Kidney Int Rep 2017;3:56)
Uses by pathologists
- DNAJB9 IHC is used as a sensitive (98%) and specific (> 99%) marker for fibrillary glomerulonephritis (Kidney Int Rep 2017;3:56)
Prognostic factors
- Fibrillary glomerulonephritis has an overall poor prognosis and a negative correlation has been demonstrated between serum DNAJB9 values and estimated glomerular filtration rate (eGFR) (Kidney Int 2019;95:1269)
- Different patterns and intensities of IHC expression of DNAJB9 are not considered a prognostic factor
Microscopic (histologic) description
- Fibrillary glomerulonephritis cases show prominent smudgy extracellular stain involving the glomerular capillary walls and mesangium (Kidney Int Rep 2017;3:56)
- May also be observed in other extraglomerular compartments (Kidney Int Rep 2017;3:56)
- Tubular basement membranes
- Arteriolar / arterial intima
- Basement membrane of peritubular capillaries
Microscopic (histologic) images
Contributed by Vincenzo L'Imperio, M.D.
Fibrillary glomerulonephritis
Fibrillary glomerulonephritis, PAS
Fibrillary glomerulonephritis, Jones silver stain
Fibrillary glomerulonephritis, DNAJB9
DNAJB9+ IHC in different compartments
DNAJB9 negative IHC
Positive staining - normal
- All positive normal tissues have a mild granular cytoplasmic stain without smudgy extracellular stain, a pattern that is considered negative
- The following staining patterns have been recorded for different tissues (Kidney Int Rep 2017;3:56)
Tissue Type of granular pattern Neurons Fine to coarse Epithelial cells from gastroenteric tract Fine Enteroendocrine cells Coarse Sinusoidal endothelial liver cells Fine to coarse Acinar pancreatic cells Fine to coarse Epithelial lung cells Fine Subset of adenohypophyseal cells Fine to coarse Epithelial cells of thyroid Fine Endothelial cells of parathyroid Fine Secretory cells of adrenal medulla Fine to coarse Epithelial cells from endometrium, fallopian tube Fine Endothelial ovarian cells Fine Placental syncytiotrophoblasts Fine Alveolar and ductal epithelial cells Fine Myoepithelial cells of the mammary gland Fine Primary spermatocytes and spermatids Fine Fibromuscular stroma Fine Tubular epithelium, podocytes, mesangial cells,
endothelial cellsFine Vascular smooth muscle cell of the kidney Fine Smooth muscle cells and urothelium of
the ureterFine Skeletal muscle Fine
Lymphocytes and lymphoid system Type of granular pattern Splenic cord Fine Small lymphocytes from tonsils Fine Small lymphocytes from lymph node paracortex Fine Small lymphocytes from thymus medulla Fine
Positive staining - disease
- Fibrillary glomerulonephritis (strong smudgy extracellular stain) (Kidney Int Rep 2017;3:56)
Negative staining
- Stain is considered negative in the absence of intense smudgy extracellular staining (Kidney Int Rep 2017;3:56)
- Amyloidosis
- Diabetic fibrillosis
- Immunotactoid glomerulopathy
- Lupus nephritis
Sample pathology report
- Kidney, left, biopsy:
- Fibrillary glomerulonephritis, DNAJB9 positive, characterized by mild glomerular and tubulointerstitial chronicity (see comment)
- Comment:
- Clinical history: 65 year old female patient with hypertension presenting with an increase in serum creatinine (1.4 mg/dl, previous values not available) and subnephrotic proteinuria (1 g/24h), normal complement levels, negative autoimmunity, no monoclonal spikes. Renal biopsy is performed.
- Microscopic description: sample entirely composed of renal cortex, containing 11 glomeruli 3 of which (27%) are globally sclerosed. Mild focal and segmental expansion of the mesangial areas associated with mild and focal / segmental mesangial hypercellularity. Deposition of hyaline, amorphous material within the mesangium and some of the capillary walls. The deposits are weakly PAS positive and nonargyrophilic. Congo red is negative. Interstitial fibrosis and tubular atrophy extended to ~10% of the cortex. Mild interstitial inflammation without significant tubulitis. Rare intratubular hyaline casts. No significant arterial abnormalities.
- Immunofluorescence: Diffuse and global coarsely granular and smudgy positivity for IgG (3+), C3 (2 - 3+) with equal representation of the immunoglobulin light chains (2 - 3+) involving mesangium and capillary walls. Same positivity in some of the tubular basement membranes and peritubular capillary walls. Negativity for IgA, IgM, C3, C1q and fibrinogen.
- Electron microscopy: Presence of structured deposits composed of nonbranching, randomly oriented fibrils 12 - 20 nm in diameter localized within mesangial areas and in the subendothelial space; rarely, the deposits are seen in the subepithelial space and within the tubular and peritubular capillary basement membranes. Podocyte foot process effacement extends over 70% of the surface of the capillary loops. Glomerular basement membrane thickness is average for sex and age, assessed far from the aspects of hypercellularity, equal to ~240 nm.
- Immunohistochemistry: Diffuse and global mesangial and capillary wall positivity for DNAJB9 with intense smudgy extracellular positivity, also focally involving tubular and peritubular capillary basement membranes.
Practice question #1
Which DNAJB9 staining pattern would be considered positive for diagnosis of fibrillary glomerulonephritis (FGN)?
- Endocapillary positivity with extracellular glomerular stain
- Fine cytoplasmic granular positivity of the tubular basement membrane
- Nuclear positivity in mesangial cells
- Smudgy extracellular stain in mesangial and capillary wall
Practice answer #1
D. Smudgy extracellular stain in mesangial and capillary wall. Answer B is incorrect because although tubular basement membrane can be affected, in order to consider the stain positive for fibrillary glomerulonephritis there should also be the extracellular stain. Answer C is incorrect because the stain is cytoplasmic and not nuclear. Answer A is incorrect because even if the vascular compartment is involved, the positivity should be observed in the arterial / arteriolar intima or in the peritubular capillary basement membrane, not in the capillary lumen.
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Practice question #2
Which of the following is true about DNAJB9?
- DNAJB9 can be positive in the basement membrane of peritubular capillaries in fibrillary glomerulonephritis (FGN)
- DNAJB9 has 5 different staining patterns
- DNAJB9 is a heat shock protein (HSP) expressed only in a pathologic context
- DNAJB9 mild fine granular cytoplasmic positivity without extracellular stain is diagnostic for fibrillary glomerulonephritis
Practice answer #2
A. DNAJB9 can be positive in the basement membrane of peritubular capillaries in fibrillary glomerulonephritis (FGN). DNAJB9 could also be positive in the extraglomerular compartment, including the basement membrane of peritubular capillaries. Answer C is incorrect because DNAJB9 is a ubiquitous protein involved in protein folding, physiologically expressed in normal tissues. Answer B is incorrect because the number of different stain patterns is 2. Answer D is incorrect because a mild fine granular pattern without extracellular stain is negative for fibrillary glomerulonephritis; in order to be diagnostic, it has to be strong cytoplasmic granular stain with smudgy extracellular stain.
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