Background/Purpose: Deposit of different classes of immunoglobulins is the main feature of lupus nephritis;¹ because of its high specificity, a patient is classified as having systemic lupus erythematosus (SLE) if he or she has antinuclear or anti-dsDNA antibodies and biopsy-proven nephritis.² Granular deposition of immunoglobulins at the dermoepidermal junction [lupus band (LB)] is distinctive of SLE, but its utility for SLE diagnosis is indefinite. The main objective was to evaluate concordance of immunoglobulin deposits between kidney and skin in patients with SLE. The secondary objective was to evaluate the accuracy of the LB as a diagnostic test for SLE in patients with lupus nephritis and controls with other non-SLE nephropathies.

Methods: All patients who required kidney biopsy in the last 10 months were invited to participate in the study. From all patients who signed informed consent, kidney and non-exposed-skin biopsies were taken at the same moment and were evaluated for immunoglobulins (IgG, IgM, IgA) and complement proteins (C1q and C3) deposits. A different evaluator assessed kidney and skin biopsies; nevertheless, to assess the technique’s reliability, we obtained a weighted kappa of 0.89 (CI: 0.78-0.99) when they evaluated the same set of 20 images. Intensity of fluorescence for each biopsy specimen was graded from 0 to 4 + (negative=0, and positive= 1-4+).

Results:

Results: We included 25 patients with lupus nephritis and 28 controls (other nephropathies). In the 25 patients with lupus nephritis, IgG was positive in 23 (92%) in kidney and 13 (52%) of skin biopsies; IgA in 20 (80%) of kidney and 4 (16%) of skin biopsies; IgM 23 (92%) of kidney and 9 (36%) of skin biopsies; C3 in 24 (96%) of kidney and 3 (12%) of skin; C1q in 24 (96%) and 11 (44%) of skin biopsies. The table 1 shows the high sensitivity and specificity of kidney immunoglobulin deposits for diagnosing SLE and highlights the good specificity of C1q, IgA, and IgM deposits in the skin.

Table 1. Accuracy of immunoglobulin deposits in skin or kidney for diagnosing SLE.

 

	Sensitivity	Specificity	PPV	NPV	LR (+)	LR (-)
IgG skin	0.52 (0.20 – 0.46)	0.86 (0.67 – 0.96)	0.76 (0.50 – 0.93)	0.67 (0.49 – 0.81)	3.64 (1.36 – 9.72)	0.56 (0.36 – 0.87)
IgG kidney	0.92 (0-74 – 0.99)	0.79 (0.59 – 0.92)	0.79 (0.60 – 0.92)	0.92 (0.73 – 0.99)	4.29 (2.09 – 8.81)	0.10 (0.03 – 0.39)
IgA skin	0.47 (0.33 – 0.61)	1 (0.82 – 1.0)	1 (0.28 – 1.0)	0.57 (0.42 – 0.71)	∞	0.84 (0.71 – 1.0)
IgA kidney	0.80 (0.59 – 0.93)	0.79 (0.59 – 0.92)	0.77 (0.56 – 0.91)	0.81 (0.62 – 0.94)	3.73 (1.79 – 7.79)	0.25 (0.11 – 0.57)
IgM skin	0.36 (0.18 – 0.57)	0.93 (0.76 – 0.99)	0.82 (0.48 – 0.98)	0.62 (0.46 – 0.76)	5.04 (1.20 – 21.15)	0.69 (0.50 – 0.94)
IgM kidney	0.92 (0-74 – 0.99)	0.54 (0.34 – 0.72)	0.64 (0.46 – 0.79)	0.88 (0.64 – 0.99)	1.98 (1.31 – 3.0)	0.15 (0.04 – 0.59)
C3 skin	0.12 (0.03 – 0.31)	0.93 (0.76 – 0.99)	0.60 (0.15 – 0.95)	0.54 (0.39 – 0.69)	1.68 (0.31 – 9.25)	0.95 (0.79 – 1.13)
C3 kidney	0.96 (0.80 – 1.0)	0.68 (0.48 – 0.84)	0.73 (0.54 – 0.87)	0.95 (0.75 – 1.0)	2.99 (1.73 – 5.15)	0.06 (0.01 – 0.41)
C1q skin	0.44 (0.24 – 0.65)	1 (0.82 – 1.0)	1 (0.62 – 1.0)	0.67 (0.50 – 0.80)	∞	0.56 (0.40 – 0.79)
C1q kidney	0.96 (0.80 – 1.0)	0.79 (0.59 – 0.92)	0.80 (0.61 – 0.92)	0.96 (0.78 – 1.0)	4.48 (2.19 – 9.15)	0.05 (0.01 – 0.35)

 PPV: positive predictive value, NPV: negative predictive value, LR: likelihood ratio, (+): positive, (-): negative.

Conclusion:

Deposits of immunoglobulins are more common in kidney than skin. High specificity of LB justifies its use as a diagnostic tool for SLE; the high specificity of LB suggests its utility for SLE diagnosis.

 References.

1.        Giannakakis K, Faraggiana T. Clin Rev Allergy Immunol 2011;40(3):170–80.

2.        Petri M, et al. Arthritis Rheum 2012;64(8):2677–86.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/high-specificity-of-skin-immunoglobulin-deposits-for-diagnosing-sle-in-patients-with-lupus-nephritis/