Dengue Literature Review

Jardim2012 - Autoimmune Features DHF Case Report

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Jardim2012 - Autoimmune Features DHF Case Report

Full citation: Jardim DLF, Tsukumo DML, Angerami RN, de Carvalho Filho MA, Saad MJA. Autoimmune features caused by dengue fever: a case report. Braz J Infect Dis. 2012;16(1):92–95.

Raw file: [[raw/jardim2012.pdf]]

Summary

Jardim et al. report a single case of a 25-year-old white woman admitted to UNICAMP hospital (Campinas, São Paulo, Brazil) in May 2007 with dengue haemorrhagic fever (DHF) complicated by an unusually broad constellation of autoimmune features: ANA 1/320 with a mitotic spindle fluorescent pattern, hypocomplementaemia (C3 0.39 g/L with C4 normal at 0.33 g/L), positive cryoglobulins, LE cells in pleural fluid cytology, proteinuria (0.55 g/day), and triple serositis (right pleural effusion, pericardial effusion, ascites). She also developed disseminated intravascular coagulation (DIC) features — fibrinogen consumption to 85.5 mg% (normal 220–495), prolonged PT and APTT, and vaginal bleeding. Dengue was confirmed serologically (PanBio IgM MAC-ELISA positive; Dengue DuoCassette IgM+ and IgG+ — consistent with secondary infection) during a DENV-3 outbreak documented by the São Paulo State Department of Health.

The patient recovered over two weeks with supportive care. At follow-up, all autoimmune markers had completely normalised: ANA negative, cryoglobulins negative, C3 normalised (1.89 g/L), platelets recovered (299,000/mm³), liver enzymes near-normal. Anti-dsDNA was negative throughout. The authors argue dengue-induced immune complex formation, complement activation, and NS1 cross-reactivity with host proteins drove the autoimmune picture, and propose dengue should be included in differential diagnosis when patients present with haematological disorders and autoimmune features in endemic settings.

Study Design

  • Type: Case report
  • Sample size: n=1
  • Setting: Universidade Estadual de Campinas (UNICAMP), Campinas, São Paulo, Brazil; May 2007; DENV-3 community outbreak
  • Population: 25-year-old white woman, 5 months post-partum; secondary dengue (both IgM and IgG positive)

Key Findings

  • ANA 1/320, mitotic spindle fluorescent pattern at admission; negative at follow-up — transient dengue ANA with complete resolution, adding to the Chatterjee2024→Gawali2021→Garcia2009 trajectory data
  • Mitotic spindle ANA pattern is distinct from all other dengue ANA patterns in this wiki (AC-1/homogeneous in Gawali2021; homogeneous+cytoplasmic in Velazqueza2017; homogeneous 4+ in Rajadhyaksha2012) — targets spindle apparatus/centromere-associated proteins rather than nuclear DNA/histones
  • Cryoglobulins positive at admission; negative at follow-up — first documented cryoglobulinemia case in this wiki associated with dengue
  • Selective C3 depression (0.39 g/L; normal 0.9–1.8) with C4 normal (0.33 g/L; normal 0.1–0.4) — atypical for classic SLE-associated complement consumption (where both C3 and C4 are depleted); C4-sparing suggests alternative or MBL pathway activation, or that classical pathway consumption was insufficient to deplete C4 at this disease stage
  • LE cells in pleural fluid cytology — requiring nuclear material release, anti-nuclear IgG coating, complement activation, and neutrophil phagocytosis; first documented in dengue pleural fluid in this wiki
  • Anti-dsDNA negative throughout, distinguishing from primary SLE diagnosis despite the clinical mimicry
  • Triple serositis: prominent right pleural effusion, thin pericardial effusion (echocardiogram-confirmed), ascites — lymphomonocytic exudate in both pleural and ascitic fluid
  • DIC: fibrinogen 85.5 mg% (normal 220–495), PT 20.2→36.4 sec, APTT 39.5→50.7 sec, haemoglobin drop, vaginal bleeding
  • Thrombocytopenia: 95,000/mm³ at admission (nadir ~94,000), recovering to 325,000 at discharge
  • Elevated ADA in ascitic (49.6 U/L) and pleural (39.8 U/L) fluid; near-normal range upper limit 40 U/L — reflecting lymphomonocytic inflammation
  • Liver injury: ALT 353, AST 370, ALP 206, γ-GT 177 U/L at admission → near-normal at follow-up
  • Proteinuria: 0.55 g/day
  • All infectious serologies (EBV, toxoplasmosis, syphilis, CMV, HIV, HBV, HCV) negative
  • Secondary infection confirmed: dengue IgM+ by MAC-ELISA; both IgM+ and IgG+ by DuoCassette

Methods Used

Entities Mentioned

  • DENV-3 (São Paulo state outbreak confirmed by Department of Health; May 2007; secondary infection context)
  • NS1 Protein (cross-reactivity with host proteins invoked as mechanism; Lin2003 and Lin2006 cited)
  • Aedes aegypti (implied vector, endemic area)

Concepts Addressed

Relevance & Notes

This is the most immunologically complex single dengue case report in this wiki: ANA 1/320 (mitotic spindle), positive cryoglobulins, LE cells in pleural fluid, selective C3 depression with normal C4, triple serositis, DIC — all co-present and all resolving completely at follow-up. The full ANA resolution distinguishes this clearly from the dengue-unmasked-SLE cases (Rajadhyaksha2012 - Dengue Evolving into SLE and Lupus Nephritis, Velazqueza2017 - SLE vs Dengue Case Series) and is the clearest illustration in this wiki of dengue producing a transient multi-autoantibody syndrome that completely resolves — directly supporting the “transient abnormal immune response” model.

Mitotic spindle ANA pattern: This is a different autoantigen class from the nuclear DNA/histone/nucleosome targets associated with homogeneous ANA patterns in other dengue cases. The mitotic spindle pattern (targeting centromere and spindle apparatus proteins such as pericentrin, NuMA, and tubulin-associated antigens) suggests dengue-induced autoantibody formation can extend beyond nuclear antigens to include cytoplasmic/mitotic apparatus targets. Whether this reflects epitope spreading from dengue-induced cell death (apoptosis releasing spindle apparatus proteins) or polyreactive IgM binding is not determinable from this case alone — the substrate used for ANA testing is not specified (HEp-2 vs. rat liver vs. other).

Cryoglobulinemia: Cryoglobulins are cold-precipitating immunoglobulins, frequently of mixed type II/III composition (IC containing IgM and IgG). Their presence alongside low C3 and serositis is mechanistically consistent with dengue’s known immune complex generation in secondary infection. HCV is the classical cause of mixed cryoglobulinemia; the negative HCV serology here establishes dengue as an independent trigger.

Selective C3 with C4-normal: In SLE-type immune complex nephritis and serositis, classical complement pathway activation typically depletes both C3 and C4. The C4-normal finding here either indicates a different complement activation route (alternative or MBL pathways; both can deplete C3 without C4), or early-stage disease where C4 has not yet been consumed. This distinguishes Jardim2012’s complement pattern from Rajadhyaksha2012 (both C3 22 mg/dL and C4 5 mg/dL severely depressed — consistent with classical pathway activation in lupus nephritis).

Brazil geography note: First source from Brazil in this wiki (Campinas, São Paulo state). Per the ≥2-source rule, no standalone Brazil country page is created; noted in the index.

Questions Raised

  1. What ANA substrate was used? The paper does not specify HEp-2 vs. rat liver — substrate type affects interpretability in the context of the Chatterjee2024/Gawali2021 trajectory data.
  2. Was LIA confirmatory testing performed? IIFA-positive, LIA-negative would be consistent with polyreactive IgM rather than disease-specific autoantibody induction (see Zhou2007 - Polyreactive Antibodies Natural Antibody Function).
  3. What was the cryoglobulin type (I/II/III)? Type II/III (mixed IC) is consistent with dengue-driven IC formation; type characterisation would clarify the mechanism.
  4. Does selective C3 depression with C4-normal distinguish dengue complement consumption from SLE complement consumption — could this be a clinically useful differential feature?
  5. Does the post-partum immune context (5 months post-partum) contribute to the severity of autoimmune features? Post-partum immune reconstitution involves a return of suppressed Th1/regulatory immunity, which could lower the threshold for autoimmune activation in a concurrent viral infection.

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