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PA8.3-5 | HLA, Transplantation, Autoimmunity & SLE — SDL Guide (Part 3)

SLE — Multisystem Clinical Features and Diagnosis

SLE predominantly affects women of childbearing age (F:M = 9:1). It is characterised by remissions and flares. The classic mnemonic for organ involvement is SOAP BRAIN MD (Serositis, Oral ulcers, Arthritis, Photosensitivity, Blood disorders, Renal, ANA, Immunologic markers, Neuropsychiatric, Malar rash, Discoid rash).

Key organ manifestations:

Skin:
• Malar (butterfly) rash — erythema over cheeks and nose bridge, sparing nasolabial folds; triggered by UV exposure.
• Discoid lupus — scarring, hyperpigmented plaques.
• Photosensitivity, oral ulcers, alopecia.

Joints:
• Non-erosive arthritis/arthralgia — most common feature; synovitis without joint destruction (unlike RA).

Kidneys — Lupus nephritis (WHO/ISN classification):
• Class I/II: minimal or mesangial — mild, often asymptomatic.
• Class III (focal proliferative) and Class IV (diffuse proliferative) — most severe; crescentic GN, nephrotic + nephritic syndrome, wire-loop lesions on EM (subendothelial deposits), full-house IF pattern (IgG, IgA, IgM, C3, C1q).
• Class V: membranous — nephrotic syndrome.
• Wire-loop lesions on light microscopy are characteristic of Class IV (thickened glomerular capillary walls due to large subendothelial immune complex deposits).

Serositis: Pleuritis, pericarditis (Libman–Sacks endocarditis — sterile verrucous vegetations on valve leaflets, pathognomonic).

Haematologic: Haemolytic anaemia (Coombs+), leucopenia, lymphopenia, thrombocytopenia.

Neuropsychiatric SLE: Psychosis, seizures, cranial neuropathies (from vasculitis or antiphospholipid antibody-related thrombosis).

Laboratory investigations:
• ANA (antinuclear antibody) — screening test; positive in >95% of SLE but not specific (also positive in other CTDs, drugs, healthy individuals at low titre).
• Anti-dsDNA — titre correlates with disease activity; marker of nephritis risk.
• Anti-Sm — highly specific, less sensitive.
• Complement levels (C3, C4, CH50) — consumed during active disease → fall in active SLE; monitoring C3/C4 tracks flares.
• LE cell — neutrophil that has phagocytosed an opsonised nuclear material (anti-histone antibody coated nucleus); historically important but replaced by ANA testing.
• Urinalysis: proteinuria, RBC casts (indicate nephritis).

Diagnostic approach: The 2019 EULAR/ACR classification criteria use a scoring system across domains (ANA as entry criterion + weighted points for clinical and immunological features, total ≥10 = SLE). Know the concept rather than memorising all point values for undergraduate purposes.

Systemic Lupus Erythematosus: Multisystem Features and Diagnosis

Immunosuppression in Transplantation — Key Principles

Immunosuppression in Transplantation: Key Targets and Clinical Balance

Immunosuppressive therapy is essential in all solid organ transplants to prevent rejection. The principal drugs act at different steps of T-cell activation:

• Calcineurin inhibitors (ciclosporin, tacrolimus) — inhibit calcineurin → block NFAT transcription factor → suppress IL-2 gene expression → prevent T-cell proliferation. Main side effects: nephrotoxicity, hypertension, diabetes (tacrolimus), gingival hyperplasia + hirsutism (ciclosporin).
• mTOR inhibitors (sirolimus, everolimus) — block mTOR → inhibit IL-2-driven T-cell clonal expansion; also anti-proliferative for endothelial cells (useful in chronic rejection).
• Mycophenolate mofetil (MMF) — inhibits inosine monophosphate dehydrogenase → blocks de novo purine synthesis → selective inhibition of lymphocyte proliferation (lymphocytes depend more on de novo pathway than other cells).
• Corticosteroids — broad anti-inflammatory; suppress cytokine gene transcription; used as induction and rescue therapy in acute rejection.
• Biological agents — anti-IL-2 receptor (basiliximab) for induction; anti-CD20 (rituximab) for antibody-mediated rejection; anti-thymocyte globulin (ATG) for severe acute rejection.

Balance: insufficient immunosuppression → rejection; excess → opportunistic infections (CMV, Pneumocystis), post-transplant lymphoproliferative disorder (PTLD, driven by EBV), and skin cancers.