Session Information
Date: Tuesday, November 15, 2016
Title: Systemic Lupus Erythematosus – Clinical Aspects and Treatment - Poster III: Biomarkers and Nephritis
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: The nuclear dense fine speckled (DFS) pattern observed in the ANA assay on HEp-2 cells is strongly associated with autoantibodies to the 70/75kD lens epithelium derived growth factor (LEDGF). Anti-DFS70/LEDGFp75 antibodies are rarely seen as the only autoantibody in individuals with systemic autoimmune rheumatic disease (SARD). Instead, they occur in high titer in a heterogeneous array of non-SARD inflammatory and non-inflammatory diseases, and in 1-9% of the general population. In contrast, the nuclear homogeneous (HO) and coarse speckled (CS) patterns are regularly caused by autoantibodies strongly associated SARD. It is intriguing to investigate the clinical and immunological significance of this peculiar autoimmune response. This study aimed to describe the temporal behavior of DFS reactivity and to compare the associated demographic and laboratory features with those observed in patients the HO or CS patterns and in individuals with non-reagent (NR) ANA.
Methods: We conducted a retrospective analysis of laboratory and demographic associations of the DFS pattern over an 8-year period (Jan/2006 to Dec/2013) using the databank of a large clinical laboratory (average 12,000 ANA/month). We considered only records containing at least one ANA test (NR, DFS, HO or CS patterns) and at least one of the following tests: hemoglobin, CRP, ESR, ferritin, albumin, liver enzymes, glucose, serum complement components, and white/red blood cell count.
Results: 254,840 records were eligible for analysis: DFS (7.1%), HO (0.8%), CS (0.7%), NR (91.4%) The DFS pattern was associated with younger age and male gender, comparing to HO and NR results. Individuals with the DFS pattern had lower frequency of abnormal results in most laboratory parameters in comparison to those with HO or CS patterns, and closely resembled individuals with no ANA reactivity (Table 1). Longitudinal analysis showed that DFS pattern is rather stable along the years, maintaining high titer and rarely changing to other patterns or to non-reagent ANA (Table 2). Table 1 – Age, gender and frequency of abnormal and normal results for several laboratory parameters according to the ANA pattern
|
Studied Variable |
ANA PATTERN |
||||
|
DFS |
HO |
CS |
NR |
||
|
Number of cases (%) |
17,994 (7.1) |
2,115 (0.8) |
1,798 (0.7) |
232,933 (91.4) |
|
|
Demographic Data |
Male (%) |
15.1 |
11.1* |
7.7* |
25.8* |
|
Age (years) |
40.6±14.4 |
44.6±16.3* |
40.9±14.3 |
44.7±16.4* |
|
|
Hb, RBC & WBC |
Hb (%↓) |
9.7 |
27.9* |
25.4* |
10.1 |
|
Total Leucocytes (%↓) |
2.4 |
13.1* |
17.6* |
2.3 |
|
|
Neutrophils (%↓) |
3.5 |
10.4* |
14.2* |
3.9* |
|
|
Eosinophils (%↓) |
8.1 |
20.8* |
25.1* |
7.3 |
|
|
Monocytes (%↓) |
7.2 |
20.1* |
8.5 |
6.5* |
|
|
Lymphocytes (%↓) |
1.1 |
12.8* |
18.9* |
1.2 |
|
|
Inflammatory Markers |
CRP (%↑) |
35.8 |
57.1* |
45.6* |
34.8 |
|
ESR (%↑) |
65.9 |
85.5* |
90.0* |
68.7* |
|
|
Ferritin (%↑) |
18.3 |
36.3* |
34.5* |
27.7* |
|
|
Thyroid Hormones |
TSH (%↑) |
8.0 |
14.1* |
16.1 |
7.4 |
|
Free T4 (%↑) |
10.1 |
14.8 |
11.6 |
12.2* |
|
|
Cholesterol |
Total (%↑) |
14.7 |
12.3 |
9.2 |
16.7* |
|
HDL (% normal) |
89.4 |
80.6* |
77.5* |
86.4* |
|
|
VLDL (% normal) |
82.7 |
76.5 |
83.1 |
78.7* |
|
|
Liver Markers |
AST (% normal) |
93.4 |
86.7* |
84.6* |
91.6* |
|
ALT (% normal) |
86.1 |
82.8 |
84.2 |
83.9* |
|
|
Other Markers |
Glycaemia (%↑) |
13.1 |
15.2 |
10.2 |
18.6* |
|
Albumin (%↓) |
2.3 |
15.9* |
7.2* |
3.8* |
|
|
Complement System Proteins |
CH50 (% normal) |
86.7 |
60.6* |
72.6* |
86.7 |
|
C2 (% normal) |
94.8 |
77.0* |
85.2 |
94.8 |
|
|
C3 (%↓) |
1.2 |
22.9* |
11.4* |
1.4 |
|
|
C4 (%↓) |
0.3 |
18.0* |
7.8* |
0.8 |
|
|
Globulins |
Gamma globulins (%↑) |
1.9 |
19.5* |
33.9* |
2.1 |
|
IgG (%↑) |
11.8 |
36.5* |
84.6* |
13.2 |
|
(%↓) and (%↑): relative frequency of individuals with abnormally low and abnormally high values, respectively; *groups differing from DFS at p<0.001 Table 2 – Frequency of temporal changes in ANA pattern and titer in patients presenting positive ANA with DFS, HO and CS patterns
|
Studied Variable |
ANA RESULT |
|||
|
DFS |
Ho |
CS |
||
|
Positive/negative |
Change – n (%) |
285 (5.8) |
12 (2.2)* |
3 (0.8)* |
|
stability |
No Change – n (%) |
4,602 (94.2) |
545 (97.8) |
375 (99.2) |
|
Pattern stability |
Change – n (%) |
1,130 (23.1) |
268 (48.1)* |
87 (23.0) |
|
No Change – n (%) |
3,757 (76.9) |
289 (51.9) |
291 (77.0) |
|
|
Titer Stability** |
Change – n (%) |
269 (7.6) |
10 (3.6) |
5 (1.7)* |
|
No Change – n (%) |
3,293 (92.4) |
267 (96.4) |
283 (98.3) |
|
* significantly different from DFS at p<0.001 ** only for cases with no change in pattern and no change in the reagent status
Conclusion: The ANA DFS pattern represents a temporally stable humoral response, with a laboratory profile closely resembling that of individuals with non-reagent ANA and definitely distinct from those with HO or CS ANA reactivity, especially regarding inflammatory markers, serum complement components, and red/white blood cell counts.
To cite this abstract in AMA style:
Mathias A, Dellavance A, Sá J, Muramoto F, Marvulle V, Andrade LEC. Laboratory and Demographic Longitudinal Profile of a Large Cohort of Individuals Presenting with the ANA Nuclear Dense Fine Speckled Immunofluorescence Pattern [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/laboratory-and-demographic-longitudinal-profile-of-a-large-cohort-of-individuals-presenting-with-the-ana-nuclear-dense-fine-speckled-immunofluorescence-pattern/. Accessed .« Back to 2016 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/laboratory-and-demographic-longitudinal-profile-of-a-large-cohort-of-individuals-presenting-with-the-ana-nuclear-dense-fine-speckled-immunofluorescence-pattern/