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Year : 2015  |  Volume : 6  |  Issue : 1  |  Page : 279-280  

Tissue antinuclear antibodies in renal biopsies of patients with systemic connective tissue disorders

Department of Immunopathology, PGIMER, Chandigarh, India

Date of Web Publication14-Jan-2015

Correspondence Address:
Dr. Ranjana Walker Minz
Department of Immunopathology, PGIMER, Sector-12, Chandigarh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0976-9668.149250

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How to cite this article:
Chhabra S, Bharti S, Minz RW, Bhardwaj R, Pasricha N. Tissue antinuclear antibodies in renal biopsies of patients with systemic connective tissue disorders. J Nat Sc Biol Med 2015;6:279-80

How to cite this URL:
Chhabra S, Bharti S, Minz RW, Bhardwaj R, Pasricha N. Tissue antinuclear antibodies in renal biopsies of patients with systemic connective tissue disorders. J Nat Sc Biol Med [serial online] 2015 [cited 2021 Jan 25];6:279-80. Available from:


Although localization of immunoglobulins (Igs) has been observed in nuclei of nonkeratotic cells in skin biopsies from patients with systemic lupus erythematosus (SLE), reports of nuclear Ig localization or tissue antinuclear antibodies (ANA) or in vivo ANA (i.e., in vivo binding of autoantibodies to the cell nucleus) as examined by direct immunofluorescence microscopy (DIFM) in kidney are almost nonexistent from Indian subcontinent. The present retrospective study describes nuclear localization of Igs in renal biopsies from 19 patients with systemic connective tissue disorders, studied by DIFM at our department from 1998 to December 2006.

DIFM of renal biopsies from 19 patients i.e., only 0.6% of the total renal biopsies submitted over a period of 9 years revealed in vivo nuclear localization of immunoreactants. These 19 patients included clinically diagnosed 15 cases of SLE and one case of polymyositis, dermatomyositis, scleroderma and mixed connective tissue disorder each. In vivo ANA was observed in nuclei of glomerular visceral and parietal epithelium, tubular epithelium, and interstitial cells. The extent of localization varied, with very few nuclei fluorescing in one case to >60% nuclei in other case [Figure 1]. Speckled (12 biopsies) or diffuse (seven biopsies) patterns of nuclear localization were observed in these biopsies as shown in [Table 1]. ANA in vivo was found to be positive with IgG as the most common immunoreactant (18 cases) with evidence of complement activation (C 3 positivity) in one case. Serum samples from each of these patients, obtained concurrently with the biopsy, were also evaluated for the presence of ANAs by indirect immunofluorescence using Hep2 cell lines. Twelve out of 19 cases showed morphological similar pattern of ANA in vivo in kidney biopsies as well as in serum ANA on Hep 2 cell lines i.e., speckled pattern in seven and diffuse pattern in five cases [Table 1]. In remaining seven cases the pattern of nuclear localization in the kidney, was not the same as that observed for ANA using the patient's serum. Twelve out of 15 kidney biopsies from SLE patients showed lesion of lupus nephritis class-IV with some degree of tubular destruction and mild to moderate interstitial inflammation.
Figure 1: Direct immunofluorescence photomicrograph of kidney biopsy from a patient of systemic lupus erythematosus showing diffuse antinuclear antibodies (ANA) pattern in cell nuclei (ANA in vivo) (arrows) and lupus class IV lesions (*) (×400)

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Table 1: Details of the patients showing in vivo ANA in renal biopsies with serum ANA test results

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Most studies in which DIFM have been used to evaluate immune complex lesions in renal biopsies from patients with lupus nephritis have not described nuclear localization of Igs in the kidney. In vivo nuclear deposition of Igs is a true reaction in vivo between ANAs to certain specificities and cell nuclei or is an artifactual process, is still a matter of debate. [1] Some authors advocate that in patients possessing high titers of ANAs, these might diffuse from the vascular compartment of the biopsy, during sectioning and washing procedures, and localize in nuclei artifactually at the time of processing. [2],[3] However, in murine models of SLE it has been demonstrated that ANA can penetrate the intact cells and bind to nuclei in vivo. Whatever the mechanism, the phenomenon of Ig nuclear localization in renal biopsies should be noted.

We show that this phenomenon can occur in other ANA positive autoimmune diseases such as polymyositis, dermatomyositis and scleroderma. And also 1/19 cases showed complement deposition, i.e., activation of the complement cascade, triggered by the IgG and nuclear antigen complex formed in vivo. It would be interesting to study this phenomenon prospectively to see if in vivo ANA correlates with SLE disease activity scores .

   References Top

McCoy RC. Nuclear localization of immunoglobulins in renal biopsies of patients with lupus nephritis. Am J Pathol 1972;68:469-78.  Back to cited text no. 1
Paronetto F, Koffler D. Immunofluorescent localization of immunoglobulins, complement, and fibrinogen in human diseases. I. Systemic lupus erythematosus. J Clin Invest 1965;44:1657-64.  Back to cited text no. 2
Kramers K, van Bruggen MC, Rijke-Schilder TP, Dijkman HB, Hylkema MN, Croes HJ, et al. In vivo ANA is a fixation artifact: Nucleosome-complexed antinucleosome autoantibodies bind to the cell surface and are internalized. J Am Soc Nephrol 1996;7:946-54.  Back to cited text no. 3


  [Figure 1]

  [Table 1]


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