OP0361 Sole Presentation of Lupus as Autoimmune Hemolytic Anemia: A Distinct Subgroup with Refractory Anemia, Hematological-Exclusive Prognosis, and Unique Protein Profile

Abstract

Background:

Autoimmune hemolytic anemia (AIHA) is a common complication in patients with systemic lupus erythematosus (SLE), generally managed with glucocorticoids and immunosuppressive therapy. However, a subset of patients presents with AIHA as the sole manifestation, without any other symptoms or organ involvement. To date, the clinical characteristics and underlying molecular mechanisms of this distinct subgroup remain poorly understood.

Objectives:

This study aims to analyze the disease severity, prognosis and protein profile of the SLE patients who present solely with hemolytic anemia.

Methods:

Patients were recruited and categorized as (1) SLE patients only presented with autoimmune hemolytic anemia, without any other symptoms or organ involvement (solely SLE-AIHA, n=27), (2) SLE patients presenting with autoimmune hemolytic anemia alongside other manifestations (SLE controls, n=168), (3) patients suffering from autoimmune hemolytic anemia but not SLE (AIHA controls, n=8). The clinical characteristics of three groups, anemia related factors and prognosis of the solely SLE-AIHA group were analyzed. The expression profile of 92 inflammatory proteins in serum samples was detected by Olink Target 96 Inflammation panel.

Results:

(1) In the solely SLE-AIHA group, levels of red blood cells and hemoglobin were significantly lower, while reticulocytes and bilirubin were higher compared to SLE controls. There were significant differences in the levels of PLT, immunoglobulin, complement 3, anti-dsDNA, and AnuA among the three groups (Table 1). (2) Immunosuppressive drug was less effective in controlling AIHA in the solely SLE-AIHA group than those in SLE controls (Table 1). (3) During the 7.57±6.02 years of follow-up, only 7.7%(2/26) of the solely SLE-AIHA group developed other systemic involvement of SLE. (4) The principal component analysis (PCA) indicated that the protein profile of the solely SLE-AIHA group was intermediated between SLE controls and AIHA controls (Figure 1A). A heatmap revealed significantly decreased levels of multiple inflammatory proteins in the solely SLE-AIHA group compared to SLE controls (Figure 1B). Six proteins were up-regulated in the SLE-AIHA patients in contrast to the AIHA controls, including IL-8, CASP-8, TNFSF14, OSM, EN-RAGE, and LAP TGF-beta-1, which contributed to cytokine signaling and leukocyte response (Figure 1C). Additionally, 21 proteins were down-regulated in the SLE-AIHA group compared with SLE controls, mainly associated with cytokine and chemokine signaling (Figure 1D). (5) Correlation analysis revealed that hemoglobin was negatively related to TNFB, CX3CL1, CCL11, DNER, AXIN1 in the solely SLE-AIHA group.

Conclusion:

SLE Patients presenting solely with hemolytic anemia, usually manifest with severe and refractory anemia, a hematological-exclusive prognosis, and a unique protein profile, indicating a distinct subgroup within SLE.

REFERENCES:

NIL. Figure 1The expression profile of serum inflammatory proteins in three groups. The expression profile of 92 inflammatory proteins in serum of solely SLE-AIHA patients (n=10) (group A), SLE controls (n=17) (group B) and AIHA controls (n=7) (group C) were detected by Olink Target 96 Inflammation. (A) principal component analysis (PCA) was performed by the MetaboAnalyst package (version 6.0) to analyze the variability of samples among different groups. (B) The heatmap of differential expression protein among three groups. (C) The barplot of differential expression protein enriched in different sets by GO analysis between the solely SLE-AIHA patients and AIHA controls. (D) The barplot of differential expression protein enriched in different sets by GO analysis between the solely SLE-AIHA patients and SLE controls. Table 1Comparison of clinical and laboratory characteristics of patients in three groupsSolely SLE-AIHA (27)SLE control (168)AIHA control (8)Solely SLE-AIHA vs SLE control (P)Solely SLE-AIHA vs AIHA control (P)Female23 (85.2%)161 (95.8%)8 (100%)0.0630.131Age38.63±14.32436.39±15.1053.88±21.580.2090.093Laboratory testsWBC (×10⁹/L)2.54±2.993.30±1.604.89±2.780.0010.056RBC (×10¹²/L)54.26±25.1674.79±23.8167.88±20.220.001*0.171Hb (g/L)99.35±89.32117.59±76.73201.88±75.410.003*0.006*PLT (×10⁹/L)16.06±13.344.37±5.6917.69±11.200.001*0.757Ret (×10⁹/L)707.37±1056.64298.82±251.51372.75±119.040.0560.383Ret (%)604.85±887.08248.60±231.06294.88±109.240.048*0.336LDH (U/L)59.13±52.8113.47±13.8657.93±26.140.001*0.951α-HBDH (U/L)13.80±10.204.54±4.3613.64±5.280.001*0.966TBil (umol/L)2.33±1.063.07±1.462.23±1.110.013*0.818DBil (umol/L)19.54±7.7419.26±8.3013.13±7.330.8660.045*IgA (g/L)2.67±3.191.37±0.944.16±9.200.046*0.664IgG (g/L)0.59±0.200.51±0.240.92±0.170.1080.001*IgM (g/L)0.11±0.070.08±0.060.15±0.080.9280.088C3 (g/L)47.57±54.50107.90±97.52-0.001*-C4 (g/L)9(33.3)82(48.8)-0.253-Anti-dsDNA+1（3.7）12（7.1）-0.767-Anti-SSA+7（25.9）42（25.0）-0.301-Anti-SSB+3（11.1）23（13.7）-0.547-Anti-U1RNP+44.51±90.20119.88±131.16-0.033*-Anti-Sm+6.53±15.6641.64±92.91-0.074-AnuA+19.75±24.0717.69±49.04-0.834-Anti-rRNP+74.12±116.4940.18±80.76-0.155-aCL+1.29±0.481.18±0.34-0.257-Anti-β₂GP1+2.54±2.993.30±1.604.89±2.780.0010.056LA+54.26±25.1674.79±23.8167.88±20.220.001*0.171Response to immunosuppressive drugCTX4/6（66.7）9/10（90.0）-0.304-MMF4/6(66.7)45/45 (100)-0.012*-CsA5/7 (71.4)13/15 (86.7)-0.378-Tac4/6 (66.7)7/7 (100.0)-0.192-RTX3/6 (50.0)5/5 (100.0)-0.240-The results of categorical variables were expressed as numeric values and percentages, and continuous variables were expressed as mean ± standard deviations. * P<0.05

Acknowledgements:

NIL.

Disclosure of Interests:

None declared. © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.